Am J Obstet Gynecol. 2015 Feb;212(2):248.e1-2.

Computed tomography-guided preoperative localization of abdominal wall endometrioma.

Moulder JK1Hobbs KA2Stavas J3Siedhoff MT2.

 

Abstract

A multiparous obese patient with prior abdominal surgeries complained of cyclic abdominal pain located near the surgical scar. A 1 cm lesion was identified on imaging. Computed tomography-guided needle localization was performed immediately before surgery. This allowed for complete excision of the abdominal wall endometrioma and resolution of the cyclic, focal abdominal pain.

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 Nov;182:38-42.

Determination of cathepsin G in endometrial tissue using a surface plasmon resonance imaging biosensor with tailored phosphonic inhibitor.

Grzywa R1Gorodkiewicz E2Burchacka E1Lesner A3Laudański P4Łukaszewski Z5Sieńczyk M6.

Abstract

OBJECTIVE:

Cathepsin G is a serine peptidase whose physiological role is mainly associated with an early immune response, anti-microbial activity as well as platelet activation or hydrolysis of coagulation factors. In addition, since the activity of cathepsin G has been associated with the development of various pathological disorders, the measurement of its activity in patient samples is of high interest. Unfortunately, the usefulness of common immunological methods is limited, since they cannot distinguish between catalytically active and inactive protease.

STUDY DESIGN:

Here we present the application of recently developed Surface Plasmon Resonance-based biosensor for the detection of active cathepsin G in human endometrium samples. The key element of the system is based on the irreversible binding of cathepsin G to its specific phosphonic-type inhibitor immobilized on the surface of the gold chip. The concentration of cathepsin G was measured in tissue samples from the group of patients with endometriosis as well as in the control group.

RESULTS:

The level of cathepsin G ascertained in endometrium tissue samples was over twice as high for the group of patients suffering from endometriosis as compared to the control group, with the median values of 0.5 pmol/mg and 0.2 pmol/mg, respectively.

CONCLUSION:

The SPR sensor armed with a specific irreversible phosphonic inhibitor represents a highly useful tool for the determination of catalytically active cathepsin G concentration in endometrial tissue.

 

 

J Minim Invasive Gynecol. 2015 Feb;22(2):163-76.

Electric morcellation-related reoperations after laparoscopic myomectomy and nonmyomectomy procedures.

Pereira N1Buchanan TR2Wishall KM2Kim SH2Grias I3Richard SD4Della Badia CR5.

Abstract

STUDY OBJECTIVE:

To identify, collate, and summarize the most common causes and pathologies of electric morcellation-related reoperations after laparoscopic myomectomy and nonmyomectomy procedures.

DESIGN:

A systematic review of published medical literature from January 1990 to February 2014 reporting morcellation-related reoperations after laparoscopic myomectomy and nonmyomectomy procedures involving the use of intracorporeal electric tissue morcellators. Publications were included in this review if patients underwent a second surgical procedure because of the onset of new clinical symptoms after a primary surgical procedure that involved intracorporeal morcellation or if histopathology of the morcellated surgical specimen revealed malignancy (Canadian Task Force classification II-3).

SETTING:

All case reports and case series were reported from community and academic hospitals in the United States and the rest of the world.

PATIENTS:

We identified 66 patients from 32 publications.

INTERVENTIONS:

Reoperation after laparoscopic myomectomy and nonmyomectomy procedures involving intracorporeal electric tissue morcellation.

MEASUREMENTS AND MAIN RESULTS:

For patients who presented with new clinical symptoms requiring reoperation, we recorded the follow-up period, nature and duration of the new symptoms, details of the second surgical procedure, intraoperative findings during the second surgical procedure, and the final histopathologic diagnosis. When histopathology of the morcellated specimen revealed malignancy, we recorded the specific type of malignancy, the corresponding surgical treatment that the patient underwent, and the follow-up period. Percentages and 95% confidence intervals were calculated for all categoric variables. Twenty-four (36.4%) patients underwent laparoscopic myomectomies, of which 19 (79.2%) and 5 (20.8%) patients required a second surgical procedure because of new clinical symptoms and the diagnosis of malignancy in the morcellated surgical specimen, respectively. Forty-two (63.6%) patients underwent laparoscopic hysterectomies; of these, 25 (59.5%) patients required a second surgical procedure because of the onset of new clinical symptoms, whereas the remaining 17 (40.5%) patients underwent a second surgical procedure because of the diagnosis of malignancy in the morcellated surgical specimen. The most common benign pathology was parasitic leiomyomata (22 patients, 33.3%). The most common malignant pathology was leiomyosarcoma (16 patients, 24.2%).

CONCLUSION:

Dispersion of tissue fragments into the peritoneal cavity at the time of morcellation continues to be a concern. It was previously thought that morcellated tissue fragments are resorbed by the peritoneal cavity; however, there is some evidence highlighting the long-term sequelae related to the growth and propagation of these dispersed tissue fragments in the form of parasitic leiomyomata, iatrogenic endometriosis, and cancer progression. Yet, the majority of laparoscopic myomectomy and nonmyomectomy procedures involving the use of intracorporeal electric tissue morcellators are uncomplicated, and institutions having no women with endometriosis or cancer are very unlikely to report surgical outcomes of uneventful electric morcellation. Thus, prospective studies are still required to validate the role of electric intracorporeal tissue morcellation in the pathogenesis of parasitic leiomyomata, iatrogenic endometriosis, and cancer progression.

 

 

Geburtshilfe Frauenheilkd. 2014 Aug;74(8):733-742.

Endometriosis: Survey of Current Diagnostic and Therapeutic Options and Latest Research Work.

Juhasz-Böss I1Laschke MW2Müller F3Rosenbaum P1Baum S1Solomayer EF1Ulrich U3.

 

Abstract

in EnglishGerman

Endometriosis is one of the most frequent benign diseases in women of child-bearing age. The main symptoms are chronic upper abdominal pain and infertility. However, the aetiology and pathogenesis of endometriosis are as yet insufficiently clarified. Thus, therapy is mainly symptomatic with laparoscopic surgery being the gold standard. The aim of drug therapy is to achieve a hypo-oestrogenic condition. In cases of severe endometriosisand a desire to have children there is often an indication for assisted reproduction. The present article illustrates almost all current aspects on the diagnosis of and therapy of endometriosis. From the clinical viewpoint, emphasis is placed on the rare cases of deeply infiltrating endometriosis that are, however, accompanied with a high morbidity. Current therapeutic options in cases of infertility are also presented in more detail. Furthermore, special attention is paid to the latest research results from both clinical and basic research fields in order to demonstrate our current knowledge on the pathogenesis and, where possible, potentially related therapeutic options.

 

 

Genet Mol Res. 2014 Sep 5;13(3):7239-45.

Association between the epidermal growth factor gene polymorphism and endometriosis in women from Brazil.

Oliveira CB1Falagan-Lotsch P1Souza MG1Santos RP1Encinas F2Teles H2Lasmar RB2Duarte LB2Granjeiro JM1Penna IA3.

 

Abstract

The aim of this study was to verify the association between the epidermal growth factor (EGF) +61 G/A polymorphism and the susceptibility to endometriosis using a case-control design study. The control group included fertile women without endometriosis and the case group included endometriosis patients. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to genotype the EGF +61 G/A polymorphism. Initially, a total of 184 individuals were analyzed. After matching by ethnicity, the control group was composed of 57 individuals, while the endometriosis group was composed of 57 patients. No statistically significant associations were observed between EGF +61 variants and the risk of endometriosis development (P>0.05). This is the first study correlating the EFG +61 G/A polymorphism and endometriosis in women from Brazil, and demonstrates that EFG +61 G/A is not associated with endometriosis susceptibility in Brazilian women.

 

 

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2014 Aug;34(8):922-5.

Adjunctive treatment of GnRHa combined wenshen xiaozheng decoction in treating endometriosis after laparoscopy: a clinical observation.

Ma XPCheng CZhang ZZYe YQWan GP.

Abstract

OBJECTIVE:

To observe the therapeutic efficacy and safety of gonadotropin-releasing hormone agonist (GnRHa) combined Wenshen Xiaozheng Decoction (WXD) in auxiliary treating endometriosis after laparoscopy.

METHODS:

One hundred and thirty-four endometriosis patients with confirmative pathological diagnosis were assigned to three groups depending on whether they would receive adjuvant therapy or Chinese medicine treatment, i.e., the control group, the observation 1 group, and the observation 2 group. The 22 patients in the control group received no adjuvant therapy after laparoscopy. The 42 patients in the observation 1 group were treated with GnRHa 3.6 mg by subcutaneous injection starting from the 1st day to the 5th day of menstruation, once per 28 days. The 70 patients in the observation 2 group were treated with GnRHa 3.6 mg by subcutaneous injection in combination with WXD starting from the 1st day to the 5th day of menstruation, once per 28 days. They also took WXD for 7 doses, one cycle per every 28 days. The treatment lasted for three to six months. Serum levels of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and cancer antigen 125 (CA125), as well as clinical efficacy, and adverse drug reactions were observed before and after treatment.

RESULTS:

There was statistical difference in serum levels of E2, FSH, or LH between the control group and the observation 1 and 2 groups (P < 0.05). There was no statistical difference in serum levels of E2, FSH, or LH between the observation 1 group and the observation 2 group (P > 0.05). There was statistical difference in the clinical efficiency among the 3 groups (P < 0.05). There was statistical difference in the pre-post difference of CA125 levels among the three groups (P < 0.01). Compared with the control group, there was no statistical difference in the pre-post difference of CA125 levels between the observation 1 group and the observation 2 group (P > 0.05). No obvious adverse reaction occurred during the treatment.

CONCLUSIONS:

GnRHa combined WXD showed confirmative clinical efficacy in treating endometriosis after laparoscopy. It also could lower serum levels of E2, FSH, and LH levels. So it was an ideal solution for treatment of endometriosis.

 

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2014 Aug;34(8):926-30.

Effect of compound ezhu powder on serum levels of CA125 and CA19-9, and the expression of cyclin D protein in endometriosis patients.

Wei MCao BLLiu Y.

Abstract

OBJECTIVE:

To study the effect of Compound Ezhu Powder (CEP) on serum levels of CA125 and CA19-9, and the expression of cyclin D protein in endometriosis patients, thus providing theoretical evidence for clinical application of CEP.

METHODS:

Totally 69 all endometriosis patients underwent surgical treatment at Department of Gynecology and Obstetrics, Tianjin Nankai Hospital from January 2011 to January 2013 were randomly assigned to group A (35 cases) and group B (34 cases). Meanwhile, 30 patients with uterine fibroids who prepared for surgical treatment during the same period were recruited as the control group. Patients in group A took EZP 3 months before surgery. No treatment was given to patients in group B and the control group. The serum CA125 level and the expression of cyclin D in the ectopic endometrium and the eutopic endometrium were detected in the 3 groups before surgery.

RESULTS:

The expression of cyclin D was higher in group A and group B than in the control group (P < 0.05). The serum levels of CA125 and CA19-9 were significantly lower in group A than in group B (P < 0.05). The expression of cyclin D in the ectopic endometrium was lower in group A than in group B, but with no statistical difference (P > 0.05). The expression of cyclin D in the eutopic endometrium was significantly lower in group A than in group B with statistical difference (P < 0.05). Meanwhile, the serum CA125 level was positively correlated with the serum CA19-9 level (r = 0.45, P < 0.05).

CONCLUSIONS:

The expression of cyclin D obviously increased in endometriosis patients, which was associated with the occurrence of endometriosis. CEP could lower serum levels of CA125 and CA19-9, and down-regulate the expression level of cyclin D, indicating its roles in inhibiting the cell cycle.

 

 

Arch Gynecol Obstet. 2015 Mar;291(3):591-8.

The effects of different doses of melatonin treatment on endometrial implants in an oophorectomized rat endometriosis model.

Cetinkaya N1Attar RYildirim GFicicioglu COzkan FYilmaz BYesildaglar N.

Abstract

AIMS:

To determine the effects of different doses of melatonin treatment on endometrial implants, the activity of antioxidant enzyme superoxide dismutase (SOD), the angiogenesis factor, the vascular endothelial growth factor (VEGF) and the waste metabolite product of lipid peroxidation malondialdehyde (MDA) in an oophorectomized rat endometriosis model.

METHODS:

Thirty-two, female, non-pregnant, nulligravid Sprague-Dawley, albino rats were used in this prospective, randomized, controlled and experimental study. Endometriosis was surgically induced in oophorectomized rats, and estradiol treatment was started after the first operation and continued till the end of the study. Second look, third look and necropsy operations were performed in the 2nd, 4th and 6th weeks. Mean volumes, histological scores and biochemical parameters were evaluated throughout the study.

RESULTS:

The mean volumes of endometriotic foci were 98.8 mm(3) ± 17.2 vs. 108.2 mm(3) ± 17.5, 54.1 mm(3) ± 15.6 vs. 25.8 mm(3) ± 3.6, 42.8 mm(3) ± 10.5 vs. 32.7 mm(3) ± 6.0 and histopathological scores were 2.2 ± 0.2 vs. 1.7 ± 0.1, 2.6 ± 0.2 vs. 2.2 ± 0.2, 2.6 ± 0.1 vs. 2.7 ± 0.2 in the 10 vs. 20-mg/kg/day melatonin group at the end of the second, fourth and sixth weeks, respectively. When the groups were compared, no significant differences were seen in the histopathologic scores, SOD and VEGF levels between the groups. However, the endometriotic foci volumes were significantly decreased in both melatonin treatment groups with respect to the control group at the end of the fourth and sixth weeks. Moreover, the mean MDA levels were significantly lower in the control group than in the 10-mg/kg/day melatonin group at the end of the fourth and sixth weeks.

CONCLUSION:

Melatonin treatment resulted in the regression of endometriotic lesions in oophorectomized rats. Higher doses of melatonin treatment might be more effective in the regression of implants and improvement of histologic scores as well as in the precise evaluation of SOD, MDA and VEGF distributions in the rat experimental models.

 

 

Reprod Sci. 2015 May;22(5):527-33

Expression of Nodal, Cripto, SMAD3, phosphorylated SMAD3, and SMAD4 in the proliferative endometrium of women with endometriosis.

Cruz CD1Del Puerto HL1Rocha AL1Cavallo IK1Clarizia AD1Petraglia F2Reis FM3.

Abstract

BACKGROUND:

Nodal is a growth factor of the transforming growth factor β superfamily that is expressed in high turnover tissues, such as the human endometrium, and in several malignancies. The effects of Nodal are modulated by the coreceptor Cripto and mediated by SMAD proteins. This study evaluated the gene and protein expression of Nodal, Cripto, total and phosphorylated (p) SMAD3, and SMAD4 in the proliferative endometrium of women with and without endometriosis.

METHOD:

Total RNA was isolated and complementary DNA synthesized from eutopic endometrium of women with (n = 15) and without (n = 12) endometriosis, followed by quantitative real-time polymerase chain reaction (PCR) to evaluate the gene expression of Nodal, Cripto, SMAD3, and SMAD4. Western blot was used to evaluate the protein levels of Nodal and Cripto, and immunohistochemistry was performed to localize SMAD3, pSMAD3, and SMAD4.

RESULTS:

Although Nodal expression was unchanged in women with endometriosis, real-time PCR indicated lower gene expression of Cripto (fold change 0.27, P < .05) in the endometriosis group. This difference, however, was not maintained at protein expression level as assessed by Western blot. The immunostaining of total SMAD3 was reduced in the endometriosis group (P < .01), but the localization of pSMAD3 and the nuclear staining of SMAD4 were unchanged.

CONCLUSION:

These findings suggest that the Nodal signaling pathway has subtle changes in the endometrium of women with endometriosis, but this imbalance may not cause functional damage as it seems not to affect the nuclear expression of SMAD4.

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 Nov;182:62-5.

Serum differential proteomic analysis of endometriosis and adenomyosis by iTRAQ technique.

Xiaoyu L1Weiyuan Z2Ping J3Anxia W3Liane Z3.

Abstract

OBJECTIVE(S):

Adenomyosis and endometriosis are two different diseases, although they have similar pathogenesis and characteristic. The serum differential expressed proteins in adenomyosis and endometriosismay result from the different pathogenesis of two diseases. Proteomic technology is a useful method for detecting all the proteins in samples. We try to use isobaric tags for relative and absolute quantitation (iTRAQ) technology to explore the association between the potential pathogenesis of these two diseases and these identified proteins.

STUDY DESIGN:

The serum samples from 20 patients with adenomyosis and from 20 patients with endometriosis were analyzed using iTRAQ technology to detect the differential expression of proteins. The validation of the proteins was performed using Western blot.

RESULTS:

In the serum of women with adenomyosis and with endometriosis, 14 proteins were found differentially expressed using iTRAQ technology. Nine proteins were high-expression in adenomyosis group and four proteins increased in endometriosis group. And the differential expression proteins were validated by Western blot.

CONCLUSION(S):

The proteins increased in adenomyosis group are related to blood coagulation and complement activation effects, and the proteins high-expression in endometriosis mainly take part in the process of inflammatory response and regulation of apoptosis. The differentially expressed proteins in two groups may due to the different pathogenesis of two diseases.

 

 

Histopathology. 2015 Apr;66(5):675-84.

Pathological findings in spontaneous pneumothorax specimens: does the incidence of unexpected clinically significant findings justify routine histological examination?

Sauter JL1Butnor KJ.

Abstract

AIMS:

The utility of routine histological examination of clinically primary spontaneous pneumothorax (SPTX) specimens has been questioned. In this retrospective study, we aimed to assess the clinical significance of unexpected SPTX histopathological findings, to determine whether such findings justify routine histological examination of SPTX specimens.

METHODS AND RESULTS:

Records and slides from all SPTX resections at our institution from 2002-2012 were reviewed. Clinically significant unexpected histological findings were identified in 8.3% of 72 patients, including: one patient with lung cancer, one with endometriosis, one with Birt-Hogg-Dubé (BHD) syndrome, and three with ‘bong lung’. Detection of BHD syndrome has the potential to avert advanced renal carcinoma by identifying individuals who should undergo periodic abdominal CT screening. The cost of treating a case of advanced renal carcinoma far exceeds that of histologically examining all SPTX specimens received in a 10-year period at our institution.

CONCLUSIONS:

Gross examination alone is an inadequate evaluation of SPTX specimens. This is the first study to demonstrate that routine histological examination of SPTX specimens is justified, in that it discloses unexpected findings that are clinically significant and impact on patient management.

 

 

Abdom Imaging. 2015 Mar;40(3):587-94.

Routine vs. expert-guided transvaginal ultrasound in the diagnosis of endometriosis: a retrospective review.

Fraser MA1Agarwal SChen ISingh SS.

Abstract

OBJECTIVE:

The objective of this study is to evaluate the sensitivity of routine trans vaginal ultrasound (TVUS) compared to expert-guided transvaginal ultrasound (ETVUS) for the diagnosis of endometriosis.

METHODS:

A retrospective chart review performed at a Canadian tertiary center specializing in the diagnosis and management of endometriosis. All cases with surgically confirmed endometriosis and an ETVUS completed at a single center were included for review and compared to routine TVUS performed for the same indication.

RESULTS:

Forty cases met the inclusion criteria. Mean patient age of the study population at first surgical diagnosis was 31.2 ± 6.9 years. Dysmenorrhea (76.9 %) and chronic pelvic pain (74.3 %) were the most common presenting symptoms. Sensitivity of routine TVUS was 25 % (10/40), compared to 78 % (31/40) with ETVUS, (P < 0.01). Comparisons were made based on site of disease. Routine TVUS and ETVUS detected bladder involvement in (0/40) vs. 5 % (2/40); ureter (0/40) vs. 7.5 % (3/40); ovary 25 % (10/40) vs. 72.5 % (29/40); retrocervical area (0/40) vs. 60 % (24/40), rectosigmoid 5 % (2/40) vs. 77.5 % (31/40), respectively. Specific endometriotic lesions recognized by TVUS versus ETVUS, were: ovarian endometriomas in 25 % (10/40) vs. 45 % (18/40), adhesions leading to abnormal anatomy in 2.5 % (1/40) vs. 77.5 % (31/40); endometriotic implants or plaques in 2.5 % (1/40) vs. 70 % (28/40); and endometriotic nodules in 2.5 % (1/40) vs. 35 % (14/40), respectively. Routine TVUS diagnosis relied on the presence or absence of endometrioma (10/10), whereas ETVUS showed additional sites of disease in 97 % (30/31) patients.

CONCLUSIONS:

ETVUS is more sensitive than routine TVUS to diagnose endometriosis, identifying lesions other than endometrioma and is of assistance in surgical planning and patient counseling.

Hum Reprod. 2014 Dec;29(12):2787-93.

Risk of placenta praevia is linked to endometrial thickness in a retrospective cohort study of 4537 singleton assisted reproduction technology births.

Rombauts L1Motteram C2Berkowitz E3Fernando S4.

Abstract

STUDY QUESTION:

Is endometrial thickness measured prior to embryo transfer associated with placenta praevia?

SUMMARY ANSWER:

Following IVF, the risk of placenta praevia is increased 4-fold in women with an endometrial thickness of >12 mm compared with women with an endometrial thickness of <9 mm.

WHAT IS KNOWN ALREADY:

Placenta praevia is a serious complication of pregnancy with adverse maternal and neonatal outcomes. Placenta praevia is 2- to 6-fold more likely to occur following IVF treatment but it remains unknown what factors contribute to that increased risk.

STUDY DESIGN, SIZE, DURATION:

Retrospective cohort study involving 4007 women who had 4537 singleton assisted reproduction technology (ART) births occurring between January 2006 and June 2012 with no loss to follow-up. The primary outcome measure was the diagnosis of placenta praevia, made by the treating obstetrician on a transvaginal ultrasound in the third trimester.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Women who had singleton births following single embryo transfer performed at Monash IVF in Melbourne, Australia were included. Of the 4537 cycles leading to a singleton ART birth, 2951 were stimulated cycles with fresh embryo transfers; 355 were hormone replacement therapy frozen embryo transfers and 1231 were natural cycles with frozen embryo transfers. The dataset was analysed using binary logistic general estimating equations to calculate odds ratios for placenta praevia adjusted (aOR) for known confounders.

MAIN RESULTS AND THE ROLE OF CHANCE:

The study groups did not differ significantly in age, BMI and aetiologies of infertility prior to IVF treatment. When compared with stimulated cycles, placenta praevia was less common in women undergoing natural cycles with frozen embryo transfers (OR 0.44, 95% confidence interval (CI) 0.27-0.70, P < 0.01) but hormone replacement therapy frozen embryo transfer cycles were not associated with a lower risk (OR 0.89, 95% CI 0.48-1.63). After adjusting for confounders, smoking (aOR 2.58, 95% CI 1.07-6.24, P = 0.04, endometriosis (aOR 2.01, 95% CI 1.21-3.33, P < 0.01) and endometrial thickness remained statistically significant as independent risk factors for placenta praevia. Compared with women with an endometrial thickness of <9 mm, women with an endometrial thickness of 9-12 mm had an aOR of 2.02 (95% CI 1.12-3.65, P = 0.02) and women with an endometrial thickness >12 mm had an aOR of 3.74 (95% CI 1.90-7.34, P < 0.01). These differences remained statistically significant after performing a sensitivity analysis limited to women with no previous births.

LIMITATIONS, REASONS FOR CAUTION:

The study is retrospective in nature, not all confounders may have been accounted for and details on previous intrauterine surgery, a known risk factor, were not available. In addition, ultrasound assessments were carried out by several highly trained operators measuring the endometrial thickness, the main independent variable, in a two-dimensional plane and some inter-observer variability may therefore be present.

WIDER IMPLICATIONS OF THE FINDINGS:

The findings of a higher risk of placenta praevia in patients with endometriosis and in those that smoke are in agreement with the current literature on natural conception. There have so far been no reports of an association between endometrial thickness and placenta praevia after ART. This novel finding warrants further study to elucidate the underlying cause of the association and to assess how to minimize harm to IVF patients and their offspring. The fact that the observed increased risk is not linked to the type of embryo transfer (fresh/frozen) but to the type of endometrial preparation, suggests that the risk of placenta praevia in ART can be reduced by considering an elective frozen embryo transfer in a natural cycle, especially given the growing evidence that this strategy also provides a number of other maternal and neonatal benefits.

STUDY FUNDING/COMPETING INTERESTS:

No funding was required for this study. L.R. has a minority shareholding in Monash IVF and has received unconditional research and educational grants from MSD, Merck-Serono and Ferring. L.R. serves on an advisory board for MSD and Ferring.

 

 

 

Arch Gynecol Obstet. 2015 Apr;291(4):917-32.

Adenomyosis and endometriosis. Re-visiting their association and further insights into the mechanisms of auto-traumatisation. An MRI study.

Leyendecker G1Bilgicyildirim AInacker MStalf THuppert PMall GBöttcher BWildt L.

Abstract

PURPOSE:

In a series of publications, we had developed the concept that uterine adenomyosis and pelvic endometriosis as well as endometriotic lesions at distant sites of the body share a common pathophysiology with endometriosis constituting a secondary phenomenon. Uterine auto-traumatization and the initiation of the mechanism of tissue injury and repair (TIAR) were considered the primary events in the disease process. The present MRI study was undertaken (1) to corroborate this concept by re-visiting, in view of discrepant results in the literature, the association of adenomyosis with endometriosis and (2) to extend our views concerning the mechanisms of uterine auto-traumatization.

PATIENTS AND METHODS:

MRI was performed in 143 women attending our center, in whom, on the basis of transvaginal sonography (TVS) and historical data, such as documented endometriosis and dysmenorrhea of various degrees of severity, the presence of uterine adenomyosis was suspected. In addition to the measurement of the diameter of junctional zone (JZ) of the anterior and posterior walls in the mid-sagittal plane, the diagnosis of adenomyosis was based on visualization, in that all planes were analyzed with scrutiny. By this method of “visualization” all transient enlargement of the JZ, such as peristaltic waves of the archimyometrium and sporadic neometral contractions that might mimic adenomyotic lesions could be excluded. At the same time, this method allowed to lower the limit of detection in terms of thickness of the JZ for assured diagnosis of adenomyosis. Furthermore, the localizations of the individual lesions, their shapes and patterns were described.

RESULTS:

With the method of ‘visualization’, the diagnosis of uterine adenomyosis could be verified in 127 of the 143 patients studied. The prevalence of endometriosis in adenomyosis was 80.6% and the prevalence of adenomyosis in endometriosis was 91.1%. As concluded from their localization within the uterine wall, the adenomyotic lesions predominantly developed in the median region of the upper two-thirds of the uterine wall. Cystic cornual angle adenomyosis was a distinct phenomenon that was only observed in patients suffering from extreme primary dysmenorrhea. Aside from this, the majority of the patients complained of primary dysmenorrhea (80%). On the basis of these findings and the fact that particularly extreme primary dysmenorrhea is associated with high intrauterine pressure, menstrual ‘archimetral compression by neometral contraction’ has to be considered as an important cause of uterine auto-traumatization in addition to uterine peristalsis and hyperperistalsis. Both mechanical functions of the non-pregnant uterus exert their strongest power in the upper region of the uterus, which is compatible with the predominant localization of the adenomyotic lesions.

CONCLUSIONS:

The data confirm our previous results of a high association of adenomyosis with endometriosisand vice versa. Our view of the mechanism of uterine auto-traumatization by mechanical functions of the non-pregnant uterus has to be extended, in that ‘archimetral compression by neometral contractions’ could be realized as the predominant cause of mechanical strain to the non-pregnant uterus. The data of this study confirm our concept of the etiology and pathophysiology of adenomyosis and endometriosis in that the process of chronic proliferation and inflammation is induced at the level of the archimetra by chronic uterine auto-traumatization. Furthermore, with respect to the diagnosis of uterine adenomyosis (and consequently endometriosis) this study shows a high degree of accordance between the findings in real-time TVS and MRI.

 

 

 

Arch Esp Urol. 2014 Sep;67(7):646-9.

Bladder endometriosis: report of 7 new cases and review of the literature.

Cordeiro González P1Puñal Pereira ABlanco Gómez BLema Grille J.

Abstract

OBJECTIVE:

To describe our experience with bladder endometriosis at the Department of Urology of Complejo Hospitalario Universitario de Santiago de Compostela.

METHODS:

We performed a retrospective analysis of the cases of bladder endometriosis diagnosed during the last 11 years in our hospital, from January 2000 to December 2011.

RESULTS:

A total of 7 women, with a mean age of 32-year-old have been diagnosed by biopsy of bladder endometriosis. The most common symptoms were dysuria, suprapubic pain, urinary urgency and hematuria. All patients have undergone surgery (5 transurethral resection, 2 partial cystectomy), 6 of them were also treated with post-operative LHRH analogues.

CONCLUSIONS:

Endometriosis is a common disease in young women, but the involvement of the urinary tract is unusual. There are multiple therapeutic options; despite this there exists a high probability of recurrence.

 

 

 

Biomed Res Int. 2014;2014:618964.

ABO and Rhesus blood groups and risk of endometriosis in a French Caucasian population of 633 patients living in the same geographic area.

Borghese B1Chartier M2Souza C3Santulli P1Lafay-Pillet MC2de Ziegler D2Chapron C1.

Abstract

OBJECTIVES:

The identification of epidemiological factors increasing the risk of endometriosis could shorten the time to diagnosis. Specific blood groups may be more common in patients with endometriosis.

STUDY DESIGN:

We designed a cross-sectional study of 633 Caucasian women living in the same geographic area. Study group included 311 patients with histologically proven endometriosis. Control group included 322 patients without endometriosis as checked during surgery. Frequencies of ABO and Rhesus groups in the study and control groups were compared using univariate and multivariate analyses.

RESULTS:

We observed a higher proportion of Rh-negative women in the study group, as compared to healthy controls. Multivariate analysis showed that Rh-negative women are twice as likely to develop endometriosis(aOR = 1.90; 95% CI: 1.20-2.90). There was no significant difference in ABO group distribution between patients and controls. There was no difference when taking into account either the clinical forms (superficial endometriosis, endometrioma, and deep infiltration endometriosis) or the rAFS stages.

CONCLUSION:

Rh-negative women are twice as likely to develop endometriosis. Chromosome 1p, which contains the genes coding for the Rhesus, could also harbor endometriosis susceptibility genes.

 

 

Endocrinology. 2014 Dec;155(12):4986-99.

Molecular classification of endometriosis and disease stage using high-dimensional genomic data.

Tamaresis JS1Irwin JCGoldfien GARabban JTBurney RONezhat CDePaolo LVGiudice LC.

 

Abstract

Endometriosis (E), an estrogen-dependent, progesterone-resistant, inflammatory disorder, affects 10% of reproductive-age women. It is diagnosed and staged at surgery, resulting in an 11-year latency from symptom onset to diagnosis, underscoring the need for less invasive, less expensive approaches. Because the uterine lining (endometrium) in women with E has altered molecular profiles, we tested whether molecular classification of this tissue can distinguish and stage disease. We developed classifiers using genomic data from n = 148 archived endometrial samples from women with E or without E (normal controls or with other common uterine/pelvic pathologies) across the menstrual cycle and evaluated their performance on independent sample sets. Classifiers were trained separately on samples in specific hormonal milieu, using margin tree classification, and accuracies were scored on independent validation samples. Classification of samples from women with E or no E involved 2 binary decisions, each based on expression of specific genes. These first distinguished presence or absence of uterine/pelvic pathology and then no E from E, with the latter further classified according to severity (minimal/mild or moderate/severe). Best performing classifiers identified E with 90%-100% accuracy, were cycle phase-specific or independent, and used relatively few genes to determine disease and severity. Differential gene expression and pathway analyses revealed immune activation, altered steroid and thyroid hormone signaling/metabolism, and growth factor signaling in endometrium of women with E. Similar findings were observed with other disorders vs controls. Thus, classifier analysis of genomic data from endometrium can detect and stage pelvic E with high accuracy, dependent or independent of hormonal milieu. We propose that limited classifier candidate genes are of high value in developing diagnostics and identifying therapeutic targets. Discovery of endometrial molecular differences in the presence of E and other uterine/pelvic pathologies raises the broader biological question of their impact on the steroid hormone response and normal functions of this tissue.

 

 

Dermatol Online J. 2014 Sep 16;20(9).

Primary endometriosis: a differential diagnosis with the umbilical nodular lesions.

 

Vilas Sueiro A1Monteagudo BSuárez Amor ÓRodríguez Pazos LGonzález Vilas DPérez Valcárcel Jde las Heras C.

 

Abstract

The onset of umbilical nodules with no previous abdominal surgeries or known endometriosis in other locations characterizes primary umbilical endometriosis. We present a 43-year-old woman with a painful umbilical nodule for several months. We report this case to emphasize the importance of the differential diagnosis of umbilical nodules, especially in women during the reproductive period.

 

 

J Sex Med. 2014 Dec;11(12):3078-84.

Bladder base tenderness in the etiology of deep dyspareunia.

Nourmoussavi M1Bodmer-Roy SMui JMawji NWilliams CAllaire CYong PJ.

Abstract

INTRODUCTION:

Bladder base tenderness can be present on pelvic exam in women with pelvic pain. However, its exact prevalence and clinical implications are not well understood.

AIM:

The aim of this study was to determine whether bladder base tenderness is associated with specific symptoms or signs in women, particularly dyspareunia.

METHODS:

Retrospective review of 189 consecutive women seen by a gynecologist in 2012 at a tertiary referral center for pelvic pain was conducted. Associations were tested between bladder base tenderness and variables on history/examination using bivariate analyses and multiple logistic regression.

MAIN OUTCOME MEASURE:

Deep dyspareunia and superficial dyspareunia (present/absent) were the main outcome measures.

RESULTS:

Bladder base tenderness was present in 34% of pelvic pain patients (65/189), which was significantly greater than the prevalence of bladder base tenderness of 3% (1/32) in a control sample of women without pelvic pain (odds ratio [OR] = 16.3, 95% confidence interval [CI] 2.17-121.7, Fisher exact test, P < 0.001). For the pelvic pain patients, on bivariate analyses, bladder base tenderness was significantly associated with deep dyspareunia (P < 0.001), superficial dyspareunia (P < 0.001), bladder symptoms (P = 0.026), abdominal wall trigger point (P < 0.001), and pelvic floor tenderness (P < 0.001). In contrast, bladder base tenderness was similarly present in women with or without endometriosis. On logistic regression, bladder base tenderness was independently associated with only deep dyspareunia (OR = 6.40, 95% CI: 1.25-32.7, P = 0.011), abdominal wall trigger point (OR = 3.44, 95% CI: 1.01-11.7, P = 0.037), and pelvic floor tenderness (OR = 8.22, 95% CI: 3.27-20.7, P < 0.001).

CONCLUSIONS:

Bladder base tenderness is present in one-third of women with pelvic pain, and contributes specifically to the symptom of deep dyspareunia. Bladder base tenderness was also associated with the presence of an abdominal wall trigger point and with pelvic floor tenderness, suggesting a myofascial etiology and/or nervous system sensitization.

 

 

J Endocrinol. 2014 Nov;223(2):203-16.

Decorin induced by progesterone plays a crucial role in suppressing endometriosis.

Ono YJ1Terai Y2Tanabe A1Hayashi A1Hayashi M1Yamashita Y1Kyo S1Ohmichi M1.

 

Abstract

Dienogest, a synthetic progestin, has been shown to be effective against endometriosis, although it is still unclear as to how it affects the ectopic endometrial cells. Decorin has been shown to be a powerful endogenous tumor repressor acting in a paracrine fashion to limit tumor growth. Our objectives were to examine the direct effects of progesterone and dienogest on the in vitro proliferation of the human ectopic endometrial epithelial and stromal cell lines, and evaluate as to how decorin contributes to this effect. We also examined DCN mRNA expression in 50 endometriosis patients. The growth of both cell lines was inhibited in a dose-dependent manner by both decorin and dienogest. Using a chromatin immunoprecipitation assay, it was noted that progesterone and dienogest directly induced the binding of the decorin promoter in the EMOsis cc/TERT cells (immortalized human ovarian epithelial cells) and CRL-4003 cells (immortalized human endometrial stromal cells). Progesterone and dienogest also led to significant induced cell cycle arrest via decorin by promoting production of p21 in both cell lines in a dose-dependent manner. Decorin also suppressed the expression of MET in both cell lines. We confirmed that DCN mRNA expression in patients treated with dienogest was higher than that in the control group. In conclusion, decorin induced by dienogest appears to play a crucial role in suppressing endometriosis by exerting anti-proliferative effects and inducing cell cycle arrest via the production of p21 human ectopic endometrial cells and eutopic endometrial stromal cells.

 

 

Ann Surg Treat Res. 2014 Sep;87(3):144-7

Endometriosis of the appendix.

Yoon J1Lee YS1Chang HS1Park CS1.

Abstract

PURPOSE:

Endometriosis is defined as functioning endometrial tissue outside of the uterus. Endometriosis of the appendix is uncommon. Its clinical presentation varies from asymptomatic to acute abdominal pain. The aims of this study were to describe our experience of managing patients with appendiceal endometriosis and to review the clinical characteristics of this medical condition.

METHODS:

Five cases of appendiceal endometriosis diagnosed between January 2007 and December 2012 were retrospectively reviewed. Patients treated for intra-abdominal endometriosis were excluded.

RESULTS:

The mean age at diagnosis was 33.8 years old. One patient was in the second trimester of pregnancy. Two patients were asymptomatic. Three patients had clinical symptoms including two with acute pain in the right lower quadrant and one with abdominal discomfort. Four patients showed appendiceal abnormalities in imaging studies including two cases of suspected mucocele and two cases of appendiceal infection. There were no suspicions of endometriosis of the appendix based on preoperative imaging studies. Three patients underwent appendectomy due to clinical symptoms, and two underwent incidental appendectomy combined with another operation. None of the patients received adjuvant therapy.

CONCLUSION:

Appendiceal endometriosis should be included in the differential diagnosis for acute abdominal pain, especially when women of childbearing age present with clinical symptoms of acute appendicitis.

 

 

J Comput Assist Tomogr. 2014 Nov-Dec;38(6):879-84.

Magnetic resonance imaging manifestations of decidualized endometriotic cysts: comparative study with ovarian cancers associated with endometriotic cysts.

Morisawa N1Kido AKataoka MMinamiguchi SKonishi ITogashi K.

Abstract

PURPOSE:

The purpose of the study was to investigate the magnetic resonance imaging findings of decidualized endometriotic cysts in comparison with endometriotic cysts associated with ovarian cancers.

METHODS:

Eighteen decidualized endometriotic cysts and 24 ovarian cancers were retrospectively assessed on height, signal intensity of the solid component on T2- and diffusion-weighted imaging, apparent diffusion coefficient value of the solid component, size of the lesion, and signal intensity of the intracystic fluid on T1-weighted imaging.

RESULTS:

The heights of the solid components in the decidualized endometriotic cysts were inferior to 11.1 mm, significantly lower compared with the ovarian cancers. Similarly, decidualized tissues showed significantly higher signals on T2-weighted imaging and higher apparent diffusion coefficient values compared with ovarian cancers but not on diffusion-weighted imaging. The decidualized endometriotic cysts were also significantly smaller. Intracystic fluids showed higher signal in the decidualized endometriotic cysts compared with ovarian cancers on T1-weighted imaging.

CONCLUSIONS:

In pregnant subjects, the presence of endometriotic cysts with low-height solid component showing high signal intensities on T2-weighted imaging is highly indicative of decidualization.

 

 

Reprod Sci. 2014 Nov;21(11):1341-51.

Elagolix, an oral GnRH antagonist, versus subcutaneous depot medroxyprogesterone acetate for the treatment of endometriosis: effects on bone mineral density.

Carr B1Dmowski WP2O’Brien C3Jiang P4Burke J3Jimenez R3Garner E4Chwalisz K4.

 

Abstract

This randomized double-blind study, with 24-week treatment and 24-week posttreatment periods, evaluated the effects of elagolix (150 mg every day, 75 mg twice a day) versus subcutaneous depot medroxyprogesterone acetate (DMPA-SC) on bone mineral density (BMD), in women with endometriosis-associated pain (n = 252). All treatments induced minimal mean changes from baseline in BMD at week 24 (elagolix 150 mg: -0.11%/-0.47%, elagolix 75 mg: -1.29%/-1.2%, and DMPA-SC: 0.99%/-1.29% in the spine and total hip, respectively), with similar or less changes at week 48 (posttreatment). Elagolix was associated with improvements in endometriosis-associated pain, assessed with composite pelvic signs and symptoms score (CPSSS) and visual analogue scale, including statistical noninferiority to DMPA-SC in dysmenorrhea and nonmenstrual pelvic pain components of the CPSSS. The most common adverse events (AEs) in elagolix groups were headache, nausea, and nasopharyngitis, whereas the most common AEs in the DMPA-SC group were headache, nausea, upper respiratory tract infection, and mood swings. This study showed that similar to DMPA-SC, elagolix treatment had minimal impact on BMD over a 24-week period and demonstrated similar efficacy on endometriosis-associated pain.

 

 

 

Reproduction. 2015 Jan;149(1):R15-33.

Antiprogestins in gynecological diseases.

Goyeneche AA1Telleria CM2.

 

Abstract

Antiprogestins constitute a group of compounds, developed since the early 1980s, that bind progesterone receptors with different affinities. The first clinical uses for antiprogestins were in reproductive medicine, e.g., menstrual regulation, emergency contraception, and termination of early pregnancies. These initial applications, however, belied the capacity for these compounds to interfere with cell growth. Within the context of gynecological diseases, antiprogestins can block the growth of and kill gynecological-related cancer cells, such as those originating in the breast, ovary, endometrium, and cervix. They can also interrupt the excessive growth of cells giving rise to benign gynecological diseases such as endometriosis and leiomyomata (uterine fibroids). In this article, we present a review of the literature providing support for the antigrowth activity that antiprogestins impose on cells in various gynecological diseases. We also provide a summary of the cellular and molecular mechanisms reported for these compounds that lead to cell growth inhibition and death. The preclinical knowledge gained during the past few years provides robust evidence to encourage the use of antiprogestins in order to alleviate the burden of gynecological diseases, either as monotherapies or as adjuvants of other therapies with the perspective of allowing for long-term treatments with tolerable side effects. The key to the clinical success of antiprogestins in this field probably lies in selecting those patients who will benefit from this therapy. This can be achieved by defining the genetic makeup required – within each particular gynecological disease – for attaining an objective response to antiprogestin-driven growth inhibition therapy.

 

 

 

 

Int J Gynecol Cancer. 2014 Nov;24(9):1590-6.

Comparison of pure and mixed-type clear cell carcinoma of the ovary: a clinicopathological analysis of 341 Chinese patients.

Ye S1You YYang JCao DBai HHuang HWu MChen JLang JShen K.

Abstract

OBJECTIVE:

This study aimed to analyze the clinicopathological features of pure and mixed-type ovarian clear cell carcinoma (CCC) in Chinese patients.

METHODS:

Patients with ovarian CCC treated in our institution between 1982 and 2012 were identified by reviewing the database and medical charts. Patients were assigned into 2 groups based on histology (pure or mixed). Comparison of clinicopathological parameters was performed to determine the similarities and/or differences between pure and mixed CCC. Kaplan-Meier model was used in survival analysis.

RESULTS:

Of 341 patients with ovarian CCC, 46 (13.5%) mixed tumors were identified, and the most common combination was clear cell/endometrioid, accounting for 56.5%. Patients with mixed-type CCC tended to have higher level of serum cancer antigen 125 (P = 0.023) and advanced tumor stage (P = 0.001). No difference was observed in other features including age, tumor size, residual disease, lymph node metastasis, and coexisting endometriosis. Tumor recurrence occurred in 47.8% and 58.1% in patients with pure and mixed histology, respectively (P = 0.209). Two groups had comparable platinum-sensitive disease (42.1% in pure and 44.0% in mixed type, P = 0.860). Patients with pure CCC had an improved median survival (105 vs 56 months), although statistical significance was not achieved. Histology subclassification of mixed tumor revealed that patients with clear cell/endometrioid histology had better survival outcome than those with clear cell/serous type (median survival, 140 vs 43 months, P = 0.004; median progression-free survival, 49 vs 12 months, P = 0.001).

CONCLUSIONS:

Patients with mixed CCC tended to have elevated serum cancer antigen 125 and advanced tumor stage. However, no significant difference was observed between the pure and mixed tumors regarding prognosis.

 

 

BMC Womens Health. 2014 Sep 26;14:117.

Role of vascular endothelial growth factor polymorphisms (-2578C>A, -460 T>C, -1154G>A, +405G>C and +936C>T) in endometriosis: a case-control study with Brazilians.

Perini JA1Cardoso JVBerardo PTVianna-Jorge RNasciutti LEBellodi-Privato MMachado DEAbrão MS.

Abstract

BACKGROUND:

Endometriosis is regarded as a complex and heterogeneous disease in which genetic and environmental factors contribute to the phenotype. The Vascular Endothelial Growth Factor (VEGF) plays important roles in the pathogenesis of endometriosis. The present study was aimed at investigating the contribution of VEGF polymorphisms as risk factors for the development of endometriosis. This is the first study to evaluate the combined influence of the five most common VEGF polymorphisms.

METHODS:

This study was conducted at two hospitals from the Brazilian public health system, and comprised 294 women submitted to laparoscopic or laparotomy surgery: 182 patients had a histologically confirmed diagnosis of endometriosis (cases), whereas 112 had no evidence of the disease (controls). The VEGF polymorphisms were determined by TaqMan real-time polymerase chain reaction. The odds ratio (OR) with their 95% confidence intervals (CI) were calculated using an unconditional logistic regression model.

RESULTS:

Endometriosis patients and controls did not differ regarding age distribution, whereas the body mass index was significantly lower in endometriosis patients, when compared with controls (23.1 ± 3.9 versus 27.3 ± 5.9, P < 0.001). The evaluation of gynecological symptoms, including dysmenorrhea, non-cyclic chronic pelvic pain, dyspareunia and infertility, indicates significantly higher prevalences among endometriosis cases. The variant allele -1154A was significantly associated with endometriosis, either considering all cases (OR: 1.90, 95% CI: 1.23-2.97), deep infiltrating endometriosis (DIE) (OR: 1.83, 95% CI: 1.16-2.90) or moderate and severe endometriosis (stages III-IV) (OR: 1.97, 95% CI: 1.21-3.19). No significant differences were found in allele or genotype distributions of the -2578C > A, -460 T > C, +405G > C and +936C > T polymorphisms between endometriosis cases and controls. A total of six haplotypes were inferred derived from four polymorphisms (-2578C > A, -460 T > C, -1154G > A and +405G > C). There was a protective association between CCGG haplotype and endometriosis, either considering all cases (OR: 0.36, 95% CI: 0.15-0.86), DIE (OR: 0.37 95% CI: 0.15 – 0.90) or stages III-IV (OR: 0.35 95% CI: 0.13 – 0.95).

CONCLUSIONS:

The present results indicate a positive association between VEGF -1154G > A and the risk of developing endometriosis, whereas the CCGG haplotype may be protective against the development of disease.

 

 

Acta Obstet Gynecol Scand. 2015 Jan;94(1):72-9.

Complications and long-term follow-up on colorectal resections in the treatment of deep infiltrating endometriosis extending to bowel wall.

Tarjanne S1Heikinheimo OMentula MHärkki P.

Abstract

OBJECTIVE:

To evaluate the rate of complications, factors associated with complications and long-term results in colorectal resections for the treatment of deep infiltrating endometriosis of the bowel wall.

DESIGN:

Retrospective study.

SETTING:

Tertiary center in Finland.

METHODS:

Medical charts were reviewed for 164 women undergoing colorectal resections for deep infiltrating endometriosis between June 2004 and December 2012 at the Department of Obstetrics and Gynecology, Helsinki University Central Hospital; in 112 women (68%) bowel resection was performed laparoscopically and in 52 women (32%) laparotomy was needed.

MAIN OUTCOME MEASURES:

Complications, re-operations, fertility.

RESULTS:

The rate of major complications was 12% for both laparoscopies and laparotomies. However, the rate of complications during laparoscopies decreased from 27% in 2004-06 to 8% between 2010 and 2012. Similarly, the complication rate in laparoscopies fell with increased personal experience of the operating surgeon. A greater size (≥4 cm) of the nodules in the resected bowel was significantly associated with the development of a major complication. During the median follow up of 61 months (range 16-116 months) 7% needed a re-operation due to recurrence. Forty-seven percent of those women who preoperatively desired a pregnancy, subsequently had a child.

CONCLUSIONS:

Laparoscopy has become a feasible alternative to laparotomy for performing colorectal resection in cases of deep infiltrating endometriosis of the bowel wall. Moreover, colorectal resections seem to result in good long-term pain relief and fertility. With increasing experience the number of complications was reduced and therefore, the practice of centralizing these operations seems to be well justified.

 

 

Hum Reprod. 2014 Nov;29(11):2413-20.

Nuclear magnetic resonance metabolomic profiling of Day 3 and 5 embryo culture medium does not predict pregnancy outcome in good prognosis patients: a prospective cohort study on single transferred embryos.

Kirkegaard K1Svane AS2Nielsen JS2Hindkjær JJ3Nielsen NC2Ingerslev HJ3.

Abstract

STUDY QUESTION:

Does the metabolomic profile, obtained with nuclear magnetic resonance (NMR), of spent culture media from human embryos correlate with reproductive potential in a cohort of good prognosis patients?

SUMMARY ANSWER:

In a large cohort of single transferred blastocysts from a homogeneous group of good prognosis patients, we find a high degree of individual variation in the metabolome that, however, has no relation to pregnancy outcome.

WHAT IS KNOWN ALREADY:

Differences among various specific metabolites have been linked to reproductive potential. Although results from retrospective near infrared (NIR) spectroscopy analyses of spent culture medias from transferred embryos were promising, randomized controlled trials were unable to demonstrate that NIR analysis improved pregnancy rates. Therefore, a more detailed investigation of the relation between embryo metabolism and reproductive potential is required. NMR is a powerful technique that provides detailed structural and dynamic information.

STUDY DESIGN, SIZE, DURATION:

A prospective cohort study was conducted at the Fertility Clinic, Aarhus University Hospital between February 2011 and July 2012. Infertile patients aged <38 years without endometriosis were offered participation and their embryos were included if greater than or equal to eight oocytes were retrieved. In total, 161 infertile patients were included in the cohort.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Spent culture media was collected on Days 3 and 5 after oocyte retrieval from 148 single transferred embryos. NMR spectra were obtained from 12 µl of spent media. Data were quantitatively analysed using multivariate analysis with respect to pregnancy outcome, defined as a live fetus by ultrasound in gestational Week 8, along with patient and treatment related variables such as embryo score, age, BMI, fertilization method and cause of infertility.

MAIN RESULTS AND THE ROLE OF CHANCE:

A total of 148 cycles were included in the analysis [embryo transfer cancelled (n = 12), no media collected (n = 1)]. Clinical pregnancy was confirmed in 47 patients (32%). We obtained high quality NMR spectra for 141 Day 3 and 137 Day 5 samples. Our spectra show a high degree of individual variation. Multivariate data analysis was performed on spectral data with several different pre-processing combinations, i.e. binning, alignment, normalization and scaling in the attempt to develop a valid prediction model. Different strategies of multivariate analysis showed, however, no correlation between the NMR profiles and pregnancy outcome, patient or treatment characteristics. No model could therefore be developed for prediction of pregnancy outcome. We conclude that within this group of good prognosis patients, large-scale metabolic variations between embryos detected with NMR have no apparent association with pregnancy outcome.

LIMITATIONS, REASONS FOR CAUTION:

Although this study is the largest we know of using NMR to investigate metabolomic profiles of single-transferred embryos, there may be differences that would be detected with a larger study. When analysing such a small sample volume, even small variations in the amount of media and dilution may introduce a large uncertainty in the results.

WIDER IMPLICATIONS OF THE FINDINGS:

Our study questions the usefulness of the entire metabolome for embryo selection, which should direct the search for viability markers in the culture media towards individual components.

STUDY FUNDING/COMPETING INTERESTS:

Funding was provided by Aarhus University, the Lippert Foundation, the Toyota Foundation, the Aase og Einar Danielsen foundation. Research at the Fertility Clinic, Aarhus Universtity Hospital is supported by an unrestricted grant from MSD and Ferring. The authors declare no competing interest.

 

 

J Pediatr Adolesc Gynecol. 2014 Dec;27(6):320-3.

Advanced stage endometriosis in adolescents and young women.

Smorgick N1As-Sanie S2Marsh CA2Smith YR2Quint EH2.

Abstract

STUDY OBJECTIVE:

To describe the prevalence and characteristics of advanced stage endometriosis in adolescents and young women treated in a tertiary referral center.

DESIGN:

Retrospective cohort.

SETTING:

Tertiary referral center.

PATIENTS AND INTERVENTIONS:

86 adolescents and young women (≤22 y) who underwent surgery for endometriosis. The operative reports were reviewed for endometriosis stage, surgical findings, surgical procedures, and pathology.

MAIN OUTCOME MEASURES:

Endometriosis stage reported according to the revised American Fertility Society classification.

RESULTS:

Early stage endometriosis (stage I or II) was found in 66 (76%) and advanced stage endometriosis(stage III or IV) in 20 (23%). The surgical findings in the 20 patients with advanced stage endometriosis included ovarian endometriomas in 14 cases, rectovaginal nodule in 1 case, and diaphragmatic and pulmonary endometriosis in 1 case. Women with advanced stage endometriosis were found to be slightly older at time of diagnosis than those with early stage disease (mean age 20.4 ± 1.4 y vs 18.7 ± 2.2 y respectively, P < .001).

CONCLUSION:

In adolescents and young women with endometriosis, advanced stage disease is not uncommon. The main presentation of advanced stage endometriosis in this age group is ovarian endometriomas rather than extensive peritoneal or adhesive disease.

 

 

J Pediatr Adolesc Gynecol. 2014 Dec;27(6):375-8.

The obstructed hemivagina, ipsilateral renal anomaly, and uterine didelphys triad and the subsequent manifestation of cervical aplasia.

Sabdia S1Sutton B2Kimble RM3.

Abstract

STUDY OBJECTIVE:

To compare a case series of the obstructed hemivagina, ipsilateral renal anomaly and uterine didelphys triad with the literature, with a focus on a subset of patients with cervical aplasia.

DESIGN, SETTING, AND PARTICIPANTS:

A retrospective case series was conducted of all patients with the triad managed between 2005-2013 at a tertiary center for adolescent gynecology.

RESULTS:

Similarities in this cohort, compared to the literature, included heterogeneity of presentation, presence of endometriosis, and asymmetry of affected side. Notable differences included 1 patient with a 16p11.2 microdeletion and 2 patients with subsequent unilateral cervical aplasia. All patients underwent magnetic resonance imaging for diagnosis. Vaginal septum division was performed in 8 cases and excision in 1 case. Both cases with cervical aplasia ultimately underwent hemi-hysterectomy, and highlight the implications of this rare variant in regards to its existence, limitations of magnetic resonance imaging in this context, and suggestions for improvement in diagnosis and management.

CONCLUSION:

The complexity of these cases, especially the evolving manifestation of cervical aplasia postoperatively, illustrates the need to recognize limitations in imaging and divergence in definitive management.

 

 

Fertil Steril. 2014 Dec;102(6):1656-62.

Comparative study of ovarian clear cell carcinoma with and without endometriosis in People’s Republic of China.

Ye S1Yang J1You Y2Cao D1Bai H1Lang J1Chen J2Shen K3.

Abstract

OBJECTIVE:

To analyze and compare the clinicopathological features and prognosis of ovarian clear cell carcinoma (CCC) with or without endometriosis in Chinese patients.

DESIGN:

Comparative study based on a retrospective review of medical charts.

SETTING:

A general university hospital.

PATIENT(S):

Two hundred ten patients diagnosed and treated with ovarian CCC between 2000 and 2012.

INTERVENTION(S):

Patients were divided into two groups depending on coexisting endometriosis. A comparison of clinicopathological characteristics was performed. The Kaplan-Meier model and Cox regression were employed in survival analysis.

MAIN OUTCOME MEASURE(S):

Clinicopathological parameters and survival outcomes.

RESULT(S):

Of 210 patients, 79 (37.6%) were confirmed to have concurrent endometriosis. Patients with endometriosis were 8 years younger than those without. They were more likely to present at early stage (78.5%) with resectable tumors in primary surgery (with optimal cytoreduction rate at 89.9%) and platinum-sensitive disease (51.7%). Median overall survival for patients with endometriosis was 115 months, an increase of 52 months when compared with 63 months for patients without endometriosis. The 5-year survival rate in patients with endometriosis was 70.2%, while it was 52.6% for those without. Univariate and multivariate analysis showed that coexisting endometriosis was not an independent predictor of survival outcome. Tumor stage and optimal debulking were the independent prognostic factors for both overall survival and progression-free survival.

CONCLUSION(S):

Patients with ovarian CCC and coexisting endometriosis had distinct clinicopathological features and better survival outcome. However, endometriosis per se did not confer improved survival.

 

 

Fertil Steril. 2014 Nov;102(5):1244-53.

World Endometriosis Research Foundation Endometriosis Phenome and Biobanking

Harmonisation Project: IV. Tissue collection, processing, and storage in endometriosis research.

Fassbender A1Rahmioglu N2Vitonis AF3Viganò P4Giudice LC5D’Hooghe TM1Hummelshoj L6Adamson GD7Becker CM8Missmer SA9Zondervan KT10WERF EPHect Working Group.

Abstract

OBJECTIVE:

To harmonize standard operating procedures (SOPs) and standardize the recording of associated data for collection, processing, and storage of human tissues relevant to endometriosis.

DESIGN:

An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries on five continents.

SETTING:

In 2013, two workshops were conducted followed by global consultation, bringing together 54 leaders in endometriosis research and sample processing from around the world.

PATIENT(S):

None.

INTERVENTION(S):

Consensus SOPs were based on: 1) systematic comparison of SOPs from 24 global centers collecting tissue samples from women with and without endometriosis on a medium or large scale (publication on >100 cases); 2) literature evidence where available, or consultation with laboratory experts otherwise; and 3) several global consultation rounds.

MAIN OUTCOME MEASURE(S):

Standard recommended and minimum required SOPs for tissue collection, processing, and storage in endometriosis research.

RESULT(S):

We developed “recommended standard” and “minimum required” SOPs for the collection, processing, and storage of ectopic and eutopic endometrium, peritoneum, and myometrium, and a biospecimen data collection form necessary for interpretation of sample-derived results.

CONCLUSION(S):

The EPHect SOPs allow endometriosis research centers to decrease variability in tissue-based results, facilitating between-center comparisons and collaborations. The procedures are also relevant to research into other gynecologic conditions involving endometrium, myometrium, and peritoneum. The consensus SOPs are based on the best available evidence; areas with limited evidence are identified as requiring further pilot studies. The SOPs will be reviewed based on investigator feedback and through systematic triannual follow-up.

 

 

Fertil Steril. 2014 Nov;102(5):1233-43.

World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: III. Fluid biospecimen collection, processing, and storage in endometriosis research.

Rahmioglu N1Fassbender A2Vitonis AF3Tworoger SS4Hummelshoj L5D’Hooghe TM2Adamson GD6Giudice LC7Becker CM8Zondervan KT9Missmer SA10WERF EPHect Working Group.

Abstract

OBJECTIVE:

To harmonize standard operating procedures (SOPs) and standardize the recording of associated data for collection, processing, and storage of fluid biospecimens relevant to endometriosis.

DESIGN:

An international collaboration involving 34 clinical/academic centers and 3 industry collaborators from 16 countries on 5 continents.

SETTING:

In 2013, 2 workshops were conducted, followed by global consultation, bringing together 54 leaders in endometriosis research and sample processing worldwide.

PATIENT(S):

None.

INTERVENTION(S):

Consensus SOPs were based on: [1] systematic comparison of SOPs from 18 global centers collecting fluid samples from women with and without endometriosis on a medium/large scale (publication on >100 cases), [2] literature evidence where available, or consultation with laboratory experts otherwise, and [3] several global consultation rounds.

MAIN OUTCOME MEASURE(S):

Standard recommended and minimum required SOPs for biofluid collection, processing, and storage in endometriosis research.

RESULT(S):

We developed recommended standard and minimum required SOPs for the collection, processing, and storage of plasma, serum, saliva, urine, endometrial/peritoneal fluid, and menstrual effluent, and a biospecimen data-collection form necessary for interpretation of sample-derived results.

CONCLUSION(S):

The Endometriosis Phenome and Biobanking Harmonisation Project SOPs allow endometriosis research centers to decrease variability in biofluid sample results, facilitating between-center comparisons and collaborations. The procedures are also relevant to research into other female conditions involving biofluid samples subject to cyclic reproductive influences. The consensus SOPs are based on the best available evidence; areas with limited evidence are identified as requiring further pilot studies. The SOPs will be reviewed based on investigator feedback, and through systematic tri-annual follow-up. Updated versions will be made available at: endometriosisfoundation.org/ephect.

 

 

Fertil Steril. 2014 Nov;102(5):1223-32.

World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: II. Clinical and covariate phenotype data collection in endometriosis research.

Vitonis AF1Vincent K2Rahmioglu N3Fassbender A4Buck Louis GM5Hummelshoj L6Giudice LC7Stratton P8Adamson GD9Becker CM10Zondervan KT11Missmer SA12WERF EPHect Working Group.

Abstract

OBJECTIVE:

To harmonize the collection of nonsurgical clinical and epidemiologic data relevant to endometriosis research, allowing large-scale collaboration.

DESIGN:

An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries on five continents.

SETTING:

In 2013, two workshops followed by global consultation, bringing together 54 leaders in endometriosis research.

PATIENTS:

None.

INTERVENTION(S):

Development of a self-administered endometriosis patient questionnaire (EPQ), based on [1] systematic comparison of questionnaires from eight centers that collect data from endometriosis cases (and controls/comparison women) on a medium to large scale (publication on >100 cases); [2] literature evidence; and [3] several global consultation rounds.

MAIN OUTCOME MEASURE(S):

Standard recommended and minimum required questionnaires to capture detailed clinical and covariate data.

RESULT(S):

The standard recommended (EPHect EPQ-S) and minimum required (EPHect EPQ-M) questionnaires contain questions on pelvic pain, subfertility and menstrual/reproductive history, hormone/medication use, medical history, and personal information.

CONCLUSION(S):

The EPQ captures the basic set of patient characteristics and exposures considered by the WERF EPHect Working Group to be most critical for the advancement of endometriosis research, but is also relevant to other female conditions with similar risk factors and/or symptomatology. The instruments will be reviewed based on feedback from investigators, and-after a first review after 1 year-triannually through systematic follow-up surveys. Updated versions will be made available through

 

 

Diagn Pathol. 2014 Sep 26;9:184.

Associations between estrogen receptor-beta polymorphisms and endometriosis risk: a meta-analysis.

Guo RZheng NDing SZheng YFeng L.

Abstract

BACKGROUND:

Many epidemiological studies have suggested an association between estrogen receptor-beta (ER-β) polymorphisms with endometriosis risk. However, the results of these studies have been inconsistent. In the present study, we performed a meta-analysis to clarify the associations between the ER-β rs4986938 and rs1256049 polymorphisms and endometriosis risk.

METHODS:

Eligible publications were retrieved from the PubMed, ISI Web of Science, and several Chinese language databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random or fixed effect model.

RESULTS:

A total of eight studies (1100 cases/1485 controls) for the rs4986938 polymorphism and four studies (353 cases/450 controls) for the rs1256049 polymorphism were included in this meta-analysis. Regarding the rs4986938 polymorphism, no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis. In the subgroup analyses by ethnicity, study sample size, endometriosis-associated infertility, and stage of endometriosis, a significantly increased risk was observed among mixed populations (dominant model, OR=2.03, 95% CI=1.56-2.64) and among cases with endometriosis-associated infertility (dominant model, OR=1.83, 95% CI=1.26-2.67). Regarding the rs1256049 polymorphism, no obvious associations were found for all genetic models in the overall population. Subgroup analyses by ethnicity and study sample size revealed that only one study of a mixed population with small sample size showed an increased risk of endometriosis. No publication bias was found in the present study.

CONCLUSIONS:

The results of this meta-analysis suggest that the ER-β rs4986938 and rs1256049 polymorphisms may not be associated with endometriosis risk, while the observed increased risk of endometriosis-associated infertility may be due to bias by the inclusion of small-scale studies.

 

 

Womens Health (Lond). 2014 Jul;10(4):431-43

Employing laparoscopic surgery for endometriosis.

Afors K1Murtada RCentini GFernandes RMeza CCastellano JWattiez A.

 

Abstract

Endometriosis is a chronic, multifactorial disease, which can impact significantly on a women’s quality of life. It is associated with pelvic pain, dyspareunia and intestinal disorders, and can lead to infertility. The use of laparoscopic surgery in the management of endometriosis is well documented; however, the optimal management of women with deep infiltrating disease remains controversial. This review describes the different surgical strategies for the treatment of endometriosis.

 

 

Int J Gynaecol Obstet. 2015 Jan;128(1):14-7.

Indications for in vitro fertilization at a public center for reproductive health in Campinas, Brazil.

Pantoja M1Fernandes A2.

Abstract

OBJECTIVE:

To assess the sociodemographic profile and gynecologic and obstetric characteristics of women referred to a public reference center in Campinas, Brazil, for in vitro fertilization (IVF).

METHODS:

Women referred between April 1, 2008, and October 31, 2009, were eligible for inclusion in a cross-sectional study. Participants were interviewed about sociodemographic characteristics, obstetric and gynecologic history, and etiologic factors resulting in the referral. Preliminary clinical examinations performed elsewhere were evaluated.

RESULTS:

A total of 176 women were included, of whom 129 (73.3%) presented with tubal factor infertility. Tubal ligation had been performed in 66 (37.5%) women. Overall, 121 (68.8%) women were aged 30 years old or less, 110 (62.5%) had received more than 8 years of schooling, 123 (69.6%) had had infertility for up to 5 years, and 99 (56.3%) did not have any children. Moreover, 25 (14.2%) women had endometriosis and 25 (14.2%) had a male factor issue. A previous ectopic pregnancy was reported for 20 (11.4%) women and pelvic inflammatory disease for 49 (27.8%).

CONCLUSION:

Tubal factor infertility was the most common indication for IVF. Preventive measures are required, in addition to policies that ensure access to high-complexity treatments in the public sector.

 

 

J Matern Fetal Neonatal Med. 2015;28(15):1795-8.

Women with endometriosis at first pregnancy have an increased risk of adverse obstetric outcome.

Conti N1Cevenini GVannuccini SOrlandini CValensise HGervasi MTGhezzi FDi Tommaso MSeveri FMPetraglia F.

Abstract

OBJECTIVE:

To evaluate pregnancy, delivery and neonatal outcome in singleton primiparous versus multiparous women with/without endometriosis.

METHODS:

Multicentric, observational and cohort study on a group of Caucasian pregnant women (n = 2239) interviewed during their hospitalization for delivery in five Italian Gynecologic and Obstetric Units (Siena, Rome, Padua, Varese and Florence).

RESULTS:

Primiparous women with endometriosis (n = 219) showed significantly higher risk of small for gestational age fetuses (OR: 2.72, 95% CI 1.46-5.06), gestational diabetes (OR: 2.13, 95% CI 1.32-3.44), preterm premature rupture of membranes (OR: 2.93, 95% CI 1.24-6.87) and preterm birth (OR: 2.24, 95% CI 1.46-3.44), and were hospitalized for a longer period of time (p < 0.0001) comparing with control group (n = 1331). Multiparous women with endometriosis (n = 97) delivered significantly more often small for gestational age fetuses (OR: 2.93, 95% CI 1.28-6.67) than control group (n = 592). Newborns of primiparous women with endometriosis needed more frequently intensive care (p = 0.05) and were hospitalized for a longer period of time (p < 0.0001).

CONCLUSIONS:

Women with endometriosis at first pregnancy have an increased risk of impaired obstetric outcome, while a reduced number of complications occur in the successive gestation. Therefore, it is worthy for obstetricians to increase the surveillance in nulliparous women with endometriosis during pregnancy.

 

 

Reprod Biomed Online. 2014 Nov;29(5):634-9.

Failure of intrauterine insemination as rescue treatment in low responders with adequate HCG timing with no oocytes retrieved.

Matorras R1Aparicio V1Corcostegui B1Prieto B1Mendoza R1Ramón O1Gomez-Picado O1Exposito A2.

 

Abstract

In this retrospective study, the efficiency of carrying out rescue intrauterine insemination (IUI) in low-responder patients undergoing IVF when no oocytes were retrieved after follicular aspiration and when HCG timing was adequate was analysed. A historical control group was used. Over 13 years, women undergoing IVF with failure to obtain oocytes at follicular aspiration underwent rescue IUI if the following criteria were met: adequate HCG timing; one normal tube; motile sperm count after preparation over 3 million/ml; and ultrasound visualization of one to six follicles over 13 mm. The rescue IUI was carried out 1 h after follicular aspiration. Results were compared with those of a standard IUI population (5394 cycles) in the same period. Confidence intervals were calculated using Poisson 97.5% confidence upper tail limits when no event was observed in the study sample. No pregnancies were achieved among the 54 cases who underwent rescue IUI (confidence interval: 0 to 6.8%). This pregnancy rate was lower than that observed in the general IUI population (17.5%) (relative risk, 19.2). After adjusting for age and endometriosis, the relative risk was 11.7. The rescue IUI is an inefficient procedure. Its efficacy is unlikely to exceed 7% pregnancy rate per IUI.

 

 

 

 

 

Obstet Gynecol Sci. 2014 Sep;57(5):343-57.

Müllerian inhibiting substance/anti-Müllerian hormone: A novel treatment for gynecologic tumors.

Kim JH1MacLaughlin DT2Donahoe PK2.

 

Abstract

Müllerian inhibiting substance (MIS), also called anti-Müllerian hormone (AMH), is a member of the transforming growth factor-β super-family of growth and differentiation response modifiers. It is produced in immature Sertoli cells in male embryos and binds to MIS/AMH receptors in primordial Müllerian ducts to cause regression of female reproductive structures that are the precursors to the fallopian tubes, the surface epithelium of the ovaries, the uterus, the cervix, and the upper third of the vagina. Because most gynecologic tumors originate from Müllerian duct-derived tissues, and since MIS/AMH causes regression of the Müllerian duct in male embryos, it is expected to inhibit the growth of gynecologic tumors. Purified recombinant human MIS/AMH causes growth inhibition of epithelial ovarian cancer cells and cell lines in vitro and in vitro via MIS receptor-mediated mechanism. Furthermore, several lines of evidence suggest that MIS/AMH inhibits proliferation in tissues and cell lines of other MIS/AMH receptor-expressing gynecologic tumors such as cervical, endometrial, breast, and in endometriosis as well. These findings indicate that bioactive MIS/AMH recombinant protein should be tested in patients against tumors expressing the MIS/AMH receptor complex, perhaps beginning with ovarian cancer because it has the worst prognosis. The molecular tools to identify MIS/AMH receptor expressing ovarian and other cancers are in place, thus, it is possible to select patients for treatment. An MIS/AMH ELISA exists to follow administered doses of MIS/AMH, as well. Clinical trials await the production of sufficient supplies of qualified recombinant human MIS/AMH for this purpose.

 

 

Minerva Chir. 2014 Oct;69(5):277-82.

Recurrence factors in women underwent laparoscopic surgery for endometrioma.

Guzel AI1Topcu HOEkilinc STokmak AKokanali MKCavkaytar SDoğanay M.

Abstract

AIM:

The aim of this paper was to assess the risk factors for endometrioma recurrence in women underwent laparoscopic surgery for endometrioma.

METHODS:

This retrospective designed study included 113 cases that underwent laparoscopic surgery for endometrioma; of these women, recurrent endometrioma was detected in 33 (29.20%) subjects and other showed no recurrence (70.80%). Age, gravidity, parity, diameter of the mass, bilaterality, previous pelvic surgery, operation type, presence of adhesions, Ca 125 levels and recurrence time was obtained from hospital records and special gynecology forms.

RESULTS:

Demographic and obstetric past history of the cases showed no statistically significant difference between the groups (P>0.05). Higher diameter of the mass, previous pelvic surgery, operation type, presence of adhesion and higher Ca 125 levels were risk factors for endometrioma recurrence (P<0.05). Receiver operator curve (ROC) analysis demonstrated that diameter of the mass, previous pelvic surgery and Ca 125 levels may be discriminative risk factors for endometrioma recurrence.

CONCLUSION:

Endometriomas ≥ 4.5 cm, especially in cases with pelvic adhesions, previous pelvic surgery and higher Ca 125 levels should be excised totally.

 

 

Gynecol Obstet Fertil. 2014 Oct;42(10):702-5.

Endometriotic lesions of the lower troncular nerves.

Niro J1Fournier M2Oberlin C3Le Tohic A2Panel P2.

 

Abstract

Although exceptional, endometriotic lesions of the troncular nerves of the lower limb may occur and are often diagnosed with delay. We report, hereby, the first case of femoral nerve endometriosis the treatment of which consisted of radical resection with femoral nerve transplant. We completed a review of the literature on sciatic nerve endometriotic lesions and discussed the physiopathology and surgical treatment.

 

 

Int J Mol Sci. 2014 Sep 29;15(10):17518-40.

A proteomic analysis of human follicular fluid: comparison between younger and older women with normal FSH levels.

Hashemitabar M1Bahmanzadeh M2Mostafaie A3Orazizadeh M4Farimani M5Nikbakht R6.

 

Abstract

The follicular fluid (FF) is produced during folliculogenesis and contains a variety of proteins that play important roles in follicle development and oocyte maturation. Age-related infertility is usually considered as a problem that can be solved by assisted reproduction technology. Therefore, the identification of novel biomarkers that are linked to reproductive aging is the subject of this study. FF was obtained from healthy younger (20-32 years old) and older (38-42 years old) women undergoing intracytoplasmic sperm injection (ICSI) due to male factor infertility. The FF was analyzed by two-dimensional gel electrophoresis (2-DE). The power of two-dimensional gel electrophoresis and the identification of proteins were exploited using matrix-assisted laser desorption-ionization time-of-flight/time-of-flight (MALDI-TOF-TOF) mass spectrometry. Twenty three protein spots showed reproducible and significant changes in the aged compared to the young group. Of these, 19 protein spots could be identified using MALDI-TOF-TOF-MS. As a result of MASCOT search, five unique downregulated proteins were identified in the older group. These were identified as serotransferrin, hemopexin precursor, complement C3, C4 and kininogen. A number of protein markers were found that may help develop diagnostic methods of infertility.

 

 

J Reprod Immunol. 2014 Dec;106:50-7.

Additional B-cell deficiency does not affect growth and angiogenesis of ectopic human endometrium in T-cell-deficient endometriosis mouse models during long-term culture.

Söhngen L1Schmidt M2Wimberger P2Kimmig R2Grümmer R3.

 

Abstract

Heterologous endometriosis mouse models characterized by transplantation of human endometrial tissue into immunodeficient mice are widely used to develop novel treatment strategies for this gynecological disease. The majority of these experiments have been performed for up to one month in athymic T-cell-deficient nude mice, which, however, still exhibit intact B-lymphocytes possibly affecting growth and persistence of the xenografts. We describe here the heterologous mouse models used so far and comparatively analyze the characteristics of human endometrial tissue after subcutaneous and intraperitoneal transplantation in nude and in Rag-1-deficient mice exhibiting T- and B-cell deficiency. Moreover, we extended the time of culturing to three months in both mouse strains. Size, histomorphology, and vascularization of xenografts of intraperitoneal and subcutaneous localization did not differ significantly nor did those of the two immunodeficient mouse strains for up to three months of culturing. Whereas the rate of lesions was similar at both localizations in nude mice, in Rag-1 knockout mice significantly more intraperitoneal than subcutaneous lesions could be recovered. Interestingly, in both mouse strains a considerable number of xenografts completely invaded the peritoneal lining after intraperitoneal transplantation and could only be recovered histomorphologically. This has to be taken into account in studies depending on the quantitative analysis of ectopic peritoneal lesions. In conclusion, T-cell deficiency seems to be sufficient for the long-term culture of human endometrial tissue in subcutaneous and intraperitoneal localizations. Additional B-cell deficiency does not provide advantages with regard to the maintenance, morphology, and blood vessel supply of the ectopic endometrial lesions.

 

 

Fertil Steril. 2014 Oct;102(4):911-21.

Computer-assisted reproductive surgery: why it matters to reproductive endocrinology and infertility subspecialists.

Gargiulo AR1.

 

Abstract

Trained fertility specialists possess a unique clinical perspective and an extensive medical and technological armamentarium to overcome reproductive dysfunction: it is their privilege and ethical duty to lead the field of reproductive surgery. However, modern reproductive surgery can no longer exist outside of the realm of advanced laparoscopy. This has been a major hurdle to the thriving of surgery within our subspecialty, owing to the time and effort required to achieve and maintain proficiency in the anti-ergonomic environment of conventional laparoscopy. Computer-assisted surgery minimizes aptitudinal restrictions to the adoption of advanced laparoscopy. As such, it promotes strategy over technique and may hold the key to the continued success of high-specialty reproductive surgery.

 

 

Cell Death Dis. 2014 Oct 2;5:e1436.

CD4+Foxp3+ regulatory T cell differentiation mediated by endometrial stromal cell-derived TECK promotes the growth and invasion of endometriotic lesions.

Li MQ1Wang Y2Chang KK3Meng YH3Liu LB4Mei J3Wang Y3Wang XQ1Jin LP1Li DJ1.

 

Abstract

Endometriosis is associated with an abnormal immune response to endometrial cells, which can facilitate the implantation and proliferation of ectopic endometrial tissue. The proportion of CD4(+)Foxp3(+) regulatory T cells (Tregs) is significantly increased in the peritoneal fluid of women with endometriosis. The thymus-expressed chemokine TECK/CCL25 directly promotes the invasiveness of endometrial stromal cells (ESCs). The aim of this study was to investigate the effects of ESC-derived TECK on the crosstalk between Tregs and ESCs in the progress of endometriosis. We determined that the percentage of Tregs and the concentration of TECK increased in the peritoneal fluid with the progression of endometriosis. The supernatant from co-cultured human ESCs and macrophages not only induced Treg differentiation and increased Treg expression of interleukin-10 (IL-10), transforming growth factor-β (TGF-β) and CD73 by activating the AKT/STAT3 signaling pathway but also repressed Treg apoptosis by downregulating Fas and FasL expression and enhanced the Treg-mediated suppression of CD4(+)CD25(-) T cells. In addition, in vitro and in vivo trials confirmed that these effects could be inhibited by anti-TECK neutralizing Abs. The secretion of IL-10 and TGF-β by Tregs increased MMP2 expression and decreased TIMP1 expression and further stimulated the proliferation and invasion of ESCs and the growth of ectopic lesions. These results indicate that TECK derived from ESCs and macrophages upregulates the number and function of Tregs in the ectopic milieu, which contributes to endometriotic immunotolerance and high levels of ESC proliferation and invasion, thereby facilitating the progression of endometriosis.

 

 

Mediators Inflamm. 2014;2014:120673.

Ecto-nucleotidases activities in the contents of ovarian endometriomas: potential biomarkers of endometriosis.

Texidó L1Romero C1Vidal A2García-Valero J3Fernández Montoli ME4Baixeras N5Condom E2Ponce J4García-Tejedor A4Martín-Satué M6.

 

Abstract

Endometriosis, defined as the growth of endometrial tissue outside the uterus, is a common gynecologic condition affecting millions of women worldwide. It is an inflammatory, estrogen-dependent complex disorder, with broad symptomatic variability, pelvic pain, and infertility being the main characteristics. Ovarian endometriomas are frequently developed in women with endometriosis. Late diagnosis is one of the main problems of endometriosis; thus, it is important to identify biomarkers for early diagnosis. The aim of the present work is to evaluate the ecto-nucleotidases activities in the contents of endometriomas. These enzymes, through the regulation of extracellular ATP and adenosine levels, are key enzymes in inflammatory processes, and their expression has been previously characterized in human endometrium. To achieve our objective, the echo-guided aspirated fluids of endometriomas were analyzed by evaluating the ecto-nucleotidases activities and compared with simple cysts. Our results show that enzyme activities are quantifiable in the ovarian cysts aspirates and that endometriomas show significantly higher ecto-nucleotidases activities than simple cysts (5.5-fold increase for ATPase and 20-fold for ADPase), thus being possible candidates for new endometriosisbiomarkers. Moreover, we demonstrate the presence of ecto-nucleotidases bearing exosomes in these fluids. These results add up to the knowledge of the physiopathologic mechanisms underlying endometriosis and, open up a promising new field of study.

 

Reprod Domest Anim. 2014 Oct;49 Suppl 4:82-7.

Physiopathologic mechanisms involved in mare endometrosis.

Rebordão MR1Galvão ASzóstek AAmaral AMateus LSkarzynski DJFerreira-Dias G.

 

Abstract

Endometrosis is a degenerative chronic process, characterized by paramount fibrosis development in mare endometrium. This condition is one of the major causes of subfertility/infertility in mares. As in other organs, fibrosis might be a pathologic sequel of many chronic inflammatory diseases. However, aetiology and physiopathologic mechanisms involved in endometrial fibrosis are still controversial. This review presents new hypotheses based on our newest data. As the first line of innate immune defence, systemic neutrophils arrive in the uterus at mating or in the presence of pathogens. A novel paradigm is that neutrophils cast out their DNA in response to infectious stimuli and form neutrophil extracellular traps (NETs). We have shown that bacterial strains of Streptococcus zooepidemicus, Escherichia coli or Staphylococcus capitis, known to cause endometritis in mares were able to induce NETs release in vitro by equine PMN to different extents. An intriguing dilemma is the dual action of NETs. While NETs play a desirable role fighting micro-organisms in mare uterus, they may also contribute to endometrial fibrosis. A long-term in vitro exposure of mare endometrium explants to NETs components (myeloperoxidase, elastase and cathepsin G) up-regulated fibrosis markers TGFβ and Tissue inhibitor of metalloproteinase (TIMP-1). Also, pro-fibrotic cytokines regulated collagen deposition and fibrosis. Changes in expression of connective tissue growth factor (CTGF), interleukins (IL)1-α, IL-1β, IL-6 and receptors in endometrium with different degrees of fibrosis and/or inflammation were observed. A putative role of CTGF, IL and NETs components in endometrosis development should be considered. Additionally, we speculate that in sustained endometritis in mares, prostaglandins may not only cause early luteolysis or early pregnancy loss, but may also be related to endometrial fibrosis pathogenesis by stimulating collagen deposition.

 

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