Minerva Ginecol. 2015 Oct;67(5):413-9.

Chronic pelvic pain, quality of life and sexual health of women treated with palmitoylethanolamide and α-lipoic acid.

Caruso S¹, Iraci Sareri M, Casella E, Ventura B, Fava V, Cianci A.

 

Abstract

AIM:

The aim of this paper was to evaluate the effects of the association between palmitoylethanolamide (PEA) and α-lipoic acid (LA) on quality of life (QoL) and sexual function in women affected by endometriosis-associated pelvic pain.

METHODS:

Fifty-six women constituted the study group and were given PEA 300 mg and LA 300mg twice daily To define the endometriosis-associated pelvic pain, the visual analogic scale (VAS) was used. The Short Form-36 (SF-36), the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS) were used to assess the QoL, the sexual function and the sexual distress, respectively. The study included three follow-ups at 3, 6 and 9 months.

RESULTS:

No changes were observed in pain, QoL and sexual function at the 3rd month follow-up (P=NS). By the 6th and 9th month, pain symptoms (P<0.001) and all categories of the QoL (P<0.001) improved. The FSFI and the FSDS scores did not change at the 3rd month follow-up (P=ns). On the contrary, at the 3rd and 9th months follow-ups they improved with respect to the baseline (P<0.001).

CONCLUSION:

The progressive reduction of the pain syndrome reported by women over the treatment period could contribute to improve the QoL and sexual life of women on PEA and LA.

 

Eur J Obstet Gynecol Reprod Biol. 2015 Dec;195:88-93.

Endometrioma size is a relevant factor in selection of the most appropriate surgical technique: a prospective randomized preliminary study.

Giampaolino P¹, Bifulco G², Di Spiezio Sardo A¹, Mercorio A¹, Bruzzese D³, Di Carlo C¹.

 

Abstract

OBJECTIVES:

To assess and compare the ovarian reserve in patients with different-sized endometriomas undergoing cystectomy or ablative surgery in order to determine the best surgical approach to safeguard healthy ovarian tissue.

STUDY DESIGN:

Prospective randomized study on 48 patients with unilateral single ovarian endometriomas. Patients were allocated into two groups based on endometrioma size: <5cm (n=26, Group A, small endometriomas) and ≥5cm (n=22, Group B, large endometriomas). Each group was randomized to coagulation or excision treatment (1:1 ratio) before the procedure. Anti-Müllerian hormone (AMH) levels were evaluated before surgery and 3 months after surgery.

RESULTS:

Both ablation and excision resulted in a significant reduction in AMH level regardless of endometrioma size. A significant interaction effect was observed between endometrioma size and type of surgical technique (analysis of covariance p for interaction=0.039): in Group A, no significant difference was found between the two surgical techniques (-17.6±4.7% vs -18.2±10.6%), whereas in Group B, the excision group showed a significantly greater percentage decrease in AMH level compared with the ablation group (-24.1±9.3% vs -14.8±6.7%, p=0.011).

CONCLUSIONS:

Both ablative and excision treatment of endometriomas have a negative effect on ovarian function. Endometrioma size is associated with the magnitude of ovarian reserve damage following excision treatment, but in the case of ablative treatment, the decrease in AMH serum level is independent of the size of the cyst. In surgical treatment of large endometriomas, the decrease in AMH level is more consistent and much more severe following cystectomy than ablation.

 

 

Fertil Steril. 2016 Jan;105(1):129-33

Second live birth after undergoing assisted reproductive technology in women operated on for endometriosis.

Boujenah J¹, Hugues JN², Sifer C³, Cedrin-Durnerin I², Bricou A², Poncelet C².

 

Abstract

OBJECTIVE:

To determine prognostic factors for a second live birth, after a first child obtained through assisted reproductive techniques (ART).

DESIGN:

Observational study from January 2004 to December 2014.

SETTING:

Tertiary care university hospital and ART center.

PATIENT(S):

A total of 164 infertile patients with endometriosis, who underwent laparoscopy surgery and had a first baby obtained by ART, were included and 65 wished a second baby.

INTERVENTION(S):

No iterative surgery.

MAIN OUTCOME MEASURE(S):

Spontaneous pregnancy rate (PR) according to endometriosis fertility index.

RESULT(S):

Among the cohort, 27 patients (41.5%) gave birth to a second child through spontaneous pregnancy, whereas 23 patients (35.3%) required ART to obtain a second live birth. No difference was observed between patients regarding age, endometriosis staging, complete removal of endometriosis lesions and pelvic adhesion, except for the least function score, and the endometriosis fertility index. Taking into account irrespective of both mode of conception a total of 78% of patients obtained a second child, with a median conception time of 17 months.

CONCLUSION(S):

The second live birth rate in infertile patients with endometriosis and with surgical treatment was high (78%). Spontaneous PR was 54%. Endometriosis fertility index could be considered as a predictive factor for a spontaneous second pregnancy in fertility management. Our results need to be confirmed in larger prospective studies.

 

 

Arch Gynecol Obstet. 2016 May;293(5):1015-22

Comparing ovarian reserve after laparoscopic excision of endometriotic cysts and hemostasis achieved either by bipolar coagulation or suturing: a randomized clinical trial.

Asgari Z¹, Rouholamin S^2,3, Hosseini R¹, Sepidarkish M⁴, Hafizi L⁵, Javaheri A⁶.

 

Abstract

PURPOSE:

This study aimed to compare ovarian reserve between laparoscopic suturing and bipolar coagulation techniques in women with unilateral endometrioma.

METHODS:

In a prospective randomized clinical trial, 109 patients with unilateral endometrioma underwent laparoscopic cystectomy. Patients were then randomized to undergo hemostasis with either bipolar coagulation (n = 57) or suturing (n = 52) technique. We evaluated the impact of surgery and hemostasis techniques on ovarian reserve using serum levels of anti-Mullerian hormone (AMH) and follicle-stimulating hormone (FSH) that were measured preoperatively and at 3 months postoperatively.

RESULTS:

Baseline characteristics such as age and preoperative AMH and FSH levels were similar between the two study groups. At 3-month follow-up, in both groups, postoperative AMH levels were significantly lower and FSH levels were significantly higher than before surgery. The decline rate of AMH levels was significantly greater in the bipolar coagulation (53.42 ± 15.28) group than in the suturing group (15.94 ± 18.55). Furthermore, patients in the suturing group had higher AMH and lower FSH as compared with the other group (p < 0.001).

CONCLUSION:

After laparoscopic stripping of endometrioma, intracorporeal suturing showed less damage on ovarian reserve as compared with bipolar electrocoagulation. Therefore, hemostatic suturing technique may be considered as a better choice after laparoscopic ovarian cystectomy.

 

 

Arch Gynecol Obstet. 2016 May;293(5):1023-31.

p53 Arg72Pro polymorphism confers the susceptibility to endometriosisamong Asian and Caucasian populations.

Lao X¹, Chen Z², Qin A³.

 

Abstract

PURPOSE:

Findings from studies on the association between the p53 Arg72Pro polymorphism and endometriosissusceptibility have so far been inconsistent. Therefore, we undertook a meta-analysis to clarify the association of p53 Arg72Pro polymorphism with the risk of endometriosis.

METHODS:

Relevant studies were chosen by searching PubMed, Embase, the Cochrane Library databases, CNKI, Wanfang database, and CBM for articles published before and up to April 30, 2015. Two independent reviewers performed the eligibility evaluation and data extraction. The odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for the overall risk estimate.

RESULTS:

Eleven case-control studies involving 1834 endometriosis cases and 2331 controls were included. Pooled data analysis suggested that the p53 72Pro variant is a significant endometriosis risk factors in comparison to the 72Arg variant (Pro vs. Arg: OR = 1.298, 95 % CI 1.082-1.558; Pro/Pro vs. Arg/Arg: OR = 1.751, 95 % CI 1.130-2.711; Pro/Arg vs. Arg/Arg: OR = 1.530, 95 % CI 1.174-1.994), which was strengthened in the dominant model (Pro/Pro + Arg/Pro vs. Arg/Arg: OR = 1.570, 95 % CI = 1.181-2.087). In the stratified analysis by ethnicity and Hardy-Weinberg equilibrium (HWE) in the controls, we found strong associations in Asians and in studies that were consistent with HWE. However, the analyses of the revised American Fertility Society (rAFS) stage and the menopausal status subgroup did not reveal any significant associations.

CONCLUSION:

In conclusion, the p53 Arg72Pro polymorphism was closely related to the risk of endometriosis, especially in Asian populations.

 

 

Case Rep Obstet Gynecol. 2015;2015

Acute Hemoperitoneum after Administration of Prostaglandin E2 for Induction of Labour.

Zhang Z¹, Lou J¹.

 

Abstract

Prostaglandin E2 is widely used in obstetrics and is thought to be relatively safe for cervical ripening and induction of labour. Here we present a case in which acute hemoperitoneum was observed after administration of prostaglandin E2 in a pregnant woman. The patient had a history of endometriosis, and a severe pelvic adhesion (ASRM stage IV) was found during her last laparoscopic surgery 3 years previously. In cases with endometriosis, use of prostaglandin E2 for induction of labour in pregnant women must be done cautiously.

 

 

J Assist Reprod Genet. 2015 Dec;32(12):1817-25.

Lipidomics analysis of follicular fluid by ESI-MS reveals potential biomarkers for ovarian endometriosis.

Cordeiro FB¹, Cataldi TR¹, Perkel KJ², do Vale Teixeira da Costa L¹, Rochetti RC¹, Stevanato J¹, Eberlin MN³, Zylbersztejn DS⁴, Cedenho AP¹, Turco EG¹.

 

Abstract

PURPOSE:

The aim of the present study was to analyze the lipid profile of follicular fluid from patients with endometriosis and endometrioma who underwent in vitro fertilization treatment (IVF).

METHODS:

The control group (n = 10) was composed of women with tubal factor or minimal male factor infertility who had positive pregnancy outcomes after IVF. The endometriosis group consisted of women with endometriosisdiagnosed by videolaparoscopy (n = 10), and from the same patients, the endometriomas fluids were collected, which composed the endometrioma group (n = 10). From the follicular fluid and endometriomas, lipids were extracted by the Bligh and Dyer method, and the samples were analyzed by tandem mass spectrometry.

RESULTS:

We observed phosphatidylglycerol phosphate, phosphatidylcholine, phosphatidylserine, and phosphatidylnositol bisphosphate in the control group. In the endometriosis group, sphingolipids and phosphatidylcholines were more abundant, while in the endometrioma group, sphingolipids and phosphatidylcholines with different m/z from the endometriosis group were found in high abundance.

CONCLUSION:

This analysis demonstrated that there is a differential representation of these lipids according to their respective groups. In addition, the lipids found are involved in important mechanisms related to endometriosis progress in the ovary. Thus, the metabolomic approach for the study of lipids may be helpful in potential biomarker discovery.

 

 

J Pathol Transl Med. 2016 Mar;50(2):155-9.

Clear Cell Adenocarcinoma Arising from Adenofibroma in a Patient with Endometriosis of the Ovary.

Cho I¹, Lim SC¹.

 

Abstract

Ovarian clear cell adenocarcinomas (CCACs) are frequently associated with endometriosis and, less often with clear cell adenofibromas (CCAFs). We encountered a case of ovarian CCAC arising from benign and borderline adenofibromas of the clear cell and endometrioid types with endometriosis in a 53-year-old woman. Regions of the adenofibromas showed transformation to CCAC and regions of the endometriosis showed atypical endometriotic cysts. This case demonstrates that CCAC can arise from CCAF or endometriosis.

 

 

Hum Reprod. 2015 Dec;30(12):2816-28.

Human endometrial epithelial telomerase is important for epithelial proliferation and glandular formation with potential implications in endometriosis.

Valentijn AJ¹, Saretzki G², Tempest N³, Critchley HO⁴, Hapangama DK⁵.

 

Abstract

STUDY QUESTION:

How does regulation of telomerase activity (TA) in human endometrial epithelial cells (EEC) by ovarian hormones impact on telomere lengths (TL) and cell proliferation?

SUMMARY ANSWER:

Healthy endometrial epithelial cell proliferation is characterized by high TA and endometrial TL changes according to the ovarian hormone cycle, with shortest TL observed in the progesterone dominant mid-secretory phase, when TA is lowest, implicating progesterone in the negative regulation of TA and TL.

WHAT IS KNOWN ALREADY:

Critical shortening of telomeres may result in permanent cell cycle arrest while the enzyme telomerase maintains telomere length (TL) and replicative capacity of cells. Telomerase expression and activity change in the human endometrium with the ovarian hormone cycle, however the effect of this on endometrial TL and cell growth is not known.

STUDY DESIGN, SIZE, DURATION:

A prospective observational study, which included endometrial and blood samples collected from 196 women.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

We studied endometrial samples from five different groups of women. Endometrial and matched blood TL and circulating steroid hormones were studied in samples collected from 85 women (Group 1). Fresh epithelial and stromal cell isolation and culture in vitro for TL and TA was done on endometrial biopsies collected from a further 74 healthy women not on hormonal therapy (Group 2) and from 5 women on medroxyprogesterone acetate (MPA) for contraception (Group 3). The epithelial TL and telomerase protein expression was examined in active, peritoneal, ectopic endometriotic and matched uterine (eutopic) endometrial samples collected from 10 women with endometriosis (Group 4); the in vivo effect of mifepristone on telomerase protein expression by immunohistochemistry (IHC) was examined in endometrium from 22 healthy women in mid-secretory phase before (n = 8), and after administering 200 mg mifepristone (n = 14) (Group 5). TA was measured by telomere repeat amplification protocol (TRAP) assay; TL by qPCR, and Q-FISH; cell proliferation was assessed by immunoblotting of histone H3 and 3D-culture to assess the ability of EECs to form spheroids; telomerase reverse transcriptase protein levels and Ki-67 (proliferative index) were assessed with IHC.

MAIN RESULTS AND THE ROLE OF CHANCE:

Endometrial TLs correlated negatively with serum progesterone levels (n = 58, r = -0.54) and were significantly longer than corresponding blood TLs (4893 ± 929 bp versus 3955 ± 557 bp, P = 0.002) suggesting a tissue-specific regulation. High TA and short TLs were observed in proliferating EECs in vivo and in vitro. During the progesterone dominant mid-secretory phase endometrial TL were significantly shorter compared with the proliferative phase (P = 0.0002). Progestagen treatment suppressed EEC TA in vivo and reduced endometrial TA in explant (P = 0.01) and in vitro cultures (P = 0.02) compared with untreated cells. Mifepristone (progesterone receptor antagonist) increased telomerase protein levels in vivo (P < 0.05). In 2D culture, Imetelstat inhibited EEC TA (P = 0.03), proliferation (P = 0.009) and in 3D culture disrupted endometrial glandular architecture (P = 0.03).

LIMITATIONS, REASONS FOR CAUTION:

The in vitro telomerase inhibition data were tested in a mono-cellular system for a short-term. Further confirmation of the results in an in vivo model is necessary. The women in group 2 included a high proportion of women although with a regular menstrual cycle, with an increased BMI (>25) therefore this may affect extrapolation of data to other groups.

WIDER IMPLICATIONS OF THE FINDINGS:

The observed effects of telomerase inhibition in vitro on epithelial cell proliferation, suggest that telomerase might be an attractive target in developing new therapies for proliferative disorders of the endometrium, such as endometriosis.

 

 

Redox Biol. 2015 Dec;6:578-86

Ovarian endometriosis-associated stromal cells reveal persistently high affinity for iron.

Mori M¹, Ito F², Shi L², Wang Y², Ishida C¹, Hattori Y³, Niwa M⁴, Hirayama T⁴, Nagasawa H⁴, Iwase A⁵, Kikkawa F⁵, Toyokuni S⁶.

 

Abstract

Ovarian endometriosis is a recognized risk for infertility and epithelial ovarian cancer, presumably due to iron overload resulting from repeated hemorrhage. To find a clue for early detection and prevention of ovarian endometriosis-associated cancer, it is mandatory to evaluate catalytic (labile) ferrous iron (catalytic Fe(II)) and to study iron manipulation in ovarian endometriotic lesions. By the use of tissues from women of ovarian endometriosis as well as endometrial tissue from women with and without endometriosis, we for the first time performed histological analysis and cellular detection of catalytic Fe(II) with a specific fluorescent probe (HMRhoNox-M), and further evaluated iron transport proteins in the human specimens and in co-culture experiments using immortalized human eutopic/ectopic endometrial stromal cells (ESCs) in the presence or absence of epithelial cells (EpCs). The amounts of catalytic Fe(II) were higher in ectopic endometrial stromal cells (ecESCs) than in normal eutopic endometrial stromal cells (n-euESCs) both in the tissues and in the corresponding immortalized ESCs. ecESCs exhibited higher transferrin receptor 1 expression both in vivo and in vitro and lower ferroportin expression in vivo than n-euESCs, leading to sustained iron uptake. In co-culture experiments of ESCs with iron-loaded EpCs, ecESCs received catalytic ferrous iron from EpCs, but n-euESCs did not. These data suggest that ecESC play a protective role for cancer-target epithelial cells by collecting excess iron, and that these characteristics are retained in the immortalized ecESCs.

 

Ultrasound Obstet Gynecol. 2016 Jun;47(6):779-83

Association between ultrasound features of adenomyosis and severity of menstrual pain.

Naftalin J¹, Hoo W¹, Nunes N¹, Holland T¹, Mavrelos D¹, Jurkovic D¹.

 

Abstract

OBJECTIVE:

To investigate the association between the ultrasound features of adenomyosis and the severity of menstrual pain.

METHODS:

This was a prospective observational study set in the general gynecology clinic of a university teaching hospital between January 2009 and January 2010. A total of 718 consecutive premenopausal women aged between 17 and 55 years attended the clinic and underwent structured clinical and transvaginal ultrasound examinations in accordance with the study protocol. Morphological features of adenomyosis on ultrasound scan were recorded systematically. A quantitative assessment of menstrual pain was made by completion of a numerical rating scale (NRS).

RESULTS:

One hundred and fifty-seven (21.9% (95% CI, 18.8-24.9%)) women were diagnosed with adenomyosis on ultrasound. Multiple linear regression analysis showed that an ultrasound diagnosis of adenomyosis and ultrasound and laparoscopic diagnoses of endometriosis were significantly associated with menstrual pain when measured by an NRS. In addition, there was a statistically significant positive correlation between the severity of menstrual pain and the number of ultrasound features of adenomyosis seen.

CONCLUSIONS:

Women with ultrasound features of adenomyosis have more severe menstrual pain than do women without these features. The positive correlation between the number of ultrasound features of adenomyosis and the severity of menstrual pain could form the basis of a clinically relevant grading system for adenomyosis. A classification of severity of adenomyosis based on the number of ultrasound features present is a novel concept that should be evaluated prospectively in different populations. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

 

 

Rare Tumors. 2015 Sep 30;7(3):5932.

A Case of Endometrioid Adenocarcinoma Originating from the Serous Surface of the Small Intestine.

Makihara N¹, Fujita I¹, Soudaf H¹, Yamamoto T², Sashikata T³, Mukohara T⁴, Maeda T⁵.

 

Abstract

Malignant transformation of endometriosis has been extensively described in the literature. However, extragonadal endometrioid adenocarcinoma, either de novo or arising from malignant transformation of endometriosis, is rare. The present case report describes a patient with endometrioid adenocarcinoma on the serous surface of the small intestine. A 25-year-old female with no history of endometriosis was referred to our hospital with an intrapelvic tumor. An internal examination, ultrasound, and magnetic resonance imaging revealed a round mass approximately 80 mm in diameter; however, identification of the affected organ was difficult. Because we could not rule out malignancy based on the non-specific radiologic findings, laparotomy was performed. A mass with ileal adhesions was detected intraoperatively. In addition, the uterus and bilateral adnexa appeared normal. The tumor was resected with part of the ileum. Histopathology confirmed a diagnosis of endometrioid adenocarcinoma originating from the serous surface of the small intestine.

 

 

J Clin Diagn Res. 2015 Sep;9(9):QD14-6

An Abdominal Wall Desmoid Tumour Mimicking Cesarean Scar Endometriomas: A Case Report and Review of the Literature.

Vural B¹, Vural F², Müezzinoglu B³.

 

Abstract

Abdominal wall desmoid tumours (DT) are rare, slow-growing benign muscular-aponeurotic fibrous tumours with the tendency to locally invade and recur. They constitute 0.03% of all neoplasms and high infiltration and recurrence rate, but there is no metastatic potential. Although surgery is the primary treatment modality, the optimal treatment remains unclear. Abdominal wall endometriosis is also an unusual disease, and preoperative clinical diagnosis is not always easy. The preoperative radiologic imaging modalities may not aid all the time. Herein, we report an abdominal mass presenting as cyclic pain. Forty-two years old woman who gave birth by cesarean section admitted the complaints of painful abdominal mass (78×45 mm in size) under her cesarean incision scar. She had severe pain, particularly during menstruation. The clinical and radiological imaging findings mimicking endometrioma. We performed wide surgical excision of mass with a 1 cm tumor-free margin with the diagnosis of a benign mesenchymal tumor in the frozen section. The postoperative course was uneventful and recovered without any complication and recurrence three years after surgery. This report presents a case of abdominal wall desmoid tumor mimicking endometrioma. In this paper, shortcomings in diagnosis, abdominal wall endometriomas, and DTs were discussed in the view of literature.

 

 

 

Clin Nucl Med. 2016 Mar;41(3):e143-5.

Endometriosis Under Estradiol Stimulation Imaged Using 18F-FDG and Its Control After Estradiol Cessation and Progesterone Hormonal Replacement.

Arsenault F¹, Turcotte É.

 

Abstract

Endometriosis is a frequent and benign cause of disabling abdominal pain, for which a diagnosis suspicion is clinically raised, but its confirmation necessitates a surgical exploration by laparoscopy. Foci of endometriosisproliferate under estrogen stimulation, like normal endometrium. We present a patient under estradiol stimulation for a history of endometrial cancer who underwent a PET/CT scan to assess an abdominal lesion showing a high F-FDG uptake, which normalized under progesterone hormonal replacement and cessation of estradiol. Two consecutive biopsies confirmed endometriosis. F-FDG evaluation of endometriosis under estrogen stimulation could be a promising approach to refractory endometriosis assessment.

 

 

Hum Mol Genet. 2016 Jan 1;25(1):97-108.

Dlx5 and Dlx6 control uterine adenogenesis during post-natal maturation: possible consequences for endometriosis.

Bellessort B¹, Le Cardinal M¹, Bachelot A², Narboux-Nême N¹, Garagnani P³, Pirazzini C³, Barbieri O⁴, Mastracci L⁵, Jonchere V¹, Duvernois-Berthet E⁶, Fontaine A¹, Alfama G¹, Levi G⁷.

 

Abstract

Dlx5 and Dlx6 are two closely associated homeobox genes which code for transcription factors involved in the control of steroidogenesis and reproduction. Inactivation of Dlx5/6 in the mouse results in a Leydig cell defect in the male and in ovarian insufficiency in the female. DLX5/6 are also strongly expressed by the human endometrium but their function in the uterus is unknown. The involvement of DLX5/6 in human uterine pathology is suggested by their strong downregulation in endometriotic lesions and upregulation in endometrioïd adenocarcinomas. We first show that Dlx5/6 expression begins in Müllerian ducts epithelia and persists then in the uterine luminal and glandular epithelia throughout post-natal maturation and in the adult. We then use a new mouse model in which Dlx5 and Dlx6 can be simultaneously inactivated in the endometrium using a Pgr(cre/+) allele. Post-natal inactivation of Dlx5/6 in the uterus results in sterility without any obvious ovarian involvement. The uteri of Pgr(cre/+); Dlx5/6(flox/flox) mice present very few uterine glands and numerous abnormally large and branched invaginations of the uterine lumen. In Dlx5/6 mutant uteri, the expression of genes involved in gland formation (Foxa2) and in epithelial remodelling during implantation (Msx1) is significantly reduced. Furthermore, we show that DLX5 is highly expressed in human endometrial glandular epithelium and that its expression is affected in endometriosis. We conclude that Dlx5 and Dlx6 expression determines uterine architecture and adenogenesis and is needed for implantation. Given their importance for female reproduction, DLX5 and DLX6 must be regarded as interesting targets for future clinical research.

 

 

Singapore Med J. 2015 Oct;56(10):573-9.

Effect of a high fat diet on ovary morphology, in vitro development, in vitro fertilisation rate and oocyte quality in mice.

Sohrabi M¹, Roushandeh AM², Alizadeh Z², Vahidinia A³, Vahabian M⁴, Hosseini M⁵.

 

Abstract

INTRODUCTION:

The aim of this study was to determine the effect of a high-fat diet (HFD) on oocyte maturation and quality in a mouse model.

METHODS:

Female BALB/c mice were allocated to one of the following groups: (a) control group (n = 40), which received a controlled diet; or (b) HFD group (n = 40), which received an HFD for 12 weeks. Sections of the ovary were examined histologically. The number of follicles and corpora lutea were counted. In vitro maturation and in vitro fertilisation (IVF) were assessed in germinal vesicle (GV) and metaphase II (MII) oocytes, respectively. The expression of bone morphogenetic protein 15 (BMP15) and leptin receptor genes in GV and MII oocytes was evaluated using reverse transcription real-time polymerase chain reactions.

RESULTS:

In the HFD group, there was a decreased number of primordial and Graafian follicles, as well as corpora lutea (p < 0.05). The rate of oocyte development to the MII stage was also reduced (p < 0.001). Cumulus expansion was observed more frequently in the control group than the HFD group (p < 0.05). The IVF rate in the HFD group was lower than that in the control group (p < 0.05). In the HFD group, BMP15 and leptin receptor genes were upregulated in the GV stage (p > 0.05) and MII stage (p < 0.05), compared to the control group.

CONCLUSION:

An HFD reduces folliculogenesis in the primordial and Graafian stages, in vitro maturation and in vitro fertilisation rates, as well as oocyte quality in mice.

 

Clin Obstet Gynecol. 2015 Dec;58(4):754-64.

Controversies in the Management of Endometrioma: To Cure Sometimes, to Treat Often, to Comfort Always?

Johnstone EB¹, Link MH.

 

Abstract

Endometriomas are common in reproductive-aged women, but controversy exists regarding their management. PubMed was searched to identify pertinent studies on outcomes of medical and surgical management of endometrioma, with focus on randomized controlled trials and meta-analyses. Surgical excision is more effective than fenestration/coagulation of endometrioma for pelvic pain but decreases antimullerian hormone. It may modestly improve the chances of spontaneous pregnancy, but does not impact chances of success with in vitro fertilization. Oral contraceptive pills improve dysmenorrhea but not dyspareunia or noncyclic pelvic pain. Management of the patient with endometrioma should be individualized based on each patient’s particular symptoms and short-term and long-term fertility goals.

 

 

Int J Mol Sci. 2015 Oct 23;16(10):25285-322.

Integrated Bioinformatics, Environmental Epidemiologic and Genomic Approaches to Identify Environmental and Molecular Links between Endometriosis and Breast Cancer.

Roy D¹, Morgan M², Yoo C³, Deoraj A⁴, Roy S⁵, Yadav VK⁶, Garoub M⁷, Assaggaf H⁸, Doke M⁹.

 

Abstract

We present a combined environmental epidemiologic, genomic, and bioinformatics approach to identify: exposure of environmental chemicals with estrogenic activity; epidemiologic association between endocrine disrupting chemical (EDC) and health effects, such as, breast cancer or endometriosis; and gene-EDC interactions and disease associations. Human exposure measurement and modeling confirmed estrogenic activity of three selected class of environmental chemicals, polychlorinated biphenyls (PCBs), bisphenols (BPs), and phthalates. Meta-analysis showed that PCBs exposure, not Bisphenol A (BPA) and phthalates, increased the summary odds ratio for breast cancer and endometriosis. Bioinformatics analysis of gene-EDC interactions and disease associations identified several hundred genes that were altered by exposure to PCBs, phthalate or BPA. EDCs-modified genes in breast neoplasms and endometriosis are part of steroid hormone signaling and inflammation pathways. All three EDCs-PCB 153, phthalates, and BPA influenced five common genes-CYP19A1, EGFR, ESR2, FOS, and IGF1-in breast cancer as well as in endometriosis. These genes are environmentally and estrogen responsive, altered in human breast and uterine tumors and endometriosis lesions, and part of Mitogen Activated Protein Kinase (MAPK) signaling pathways in cancer. Our findings suggest that breast cancer and endometriosis share some common environmental and molecular risk factors.

 

 

Int J Gynecol Cancer. 2016 Jan;26(1):52-5.

Utility Serum Marker HE4 for the Differential Diagnosis Between Endometriosisand Adnexal Malignancy.

Zapardiel I¹, Gorostidi M, Ravaggi A, Allende MT, Silveira M, Abehsera D, Macuks R.

 

Abstract

OBJECTIVE:

The aim of the study was to assess the utility of serum human epididymal secretory protein E4 (HE4) biomarker in the differential diagnosis of endometriosis and adnexal malignancies.

METHODS:

Multicentric prospective observational study between January 2010 and December 2011 in 4 European centers (Italy, Portugal, Latvia, and Spain) was carried out. We collected 981 healthy patients diagnosed with adnexal patology and selected 65 patients diagnosed with endometriosis and analyzed their serum markers CA125, HE4, and Risk of Ovarian Malignancy Algorithm (ROMA) index. We also analyzed all cases of malignant histology and divided them according to CA125 levels (negative, ≤35 U/mL; intermediate, >35-150 U/mL; and highly positive, >150 U/mL).

RESULTS:

HE4 was positive only in 1.5% of cases, CA125 in 64.6%, and ROMA index in 14.1%. In the subgroup intermediate CA125 values, positive HE4 is very specific (91.2%) correctly classifying patients with benign disease, but with lower sensibility (66.1%); however, ROMA index showed a high sensibility (89.3%), with a false-positive rate of 42.8%.

CONCLUSIONS:

HE4 can be a very useful biomarker to exclude malignant disease in patients with endometriosis.

 

 

Reprod Sci. 2016 Feb;23(2):186-91.

Endometriosis Located Proximal to or Remote From the Uterus Differentially Affects Uterine Gene Expression.

Naqvi H¹, Mamillapalli R², Krikun G¹, Taylor HS¹.

 

Abstract

The mechanisms that lead to the altered uterine gene expression in women with endometriosis are poorly understood. Are these changes in gene expression mediated by proximity to endometriotic lesions or is endometriosis a systemic disease where the effect is independent of proximity to the uterus? To answer this question, we created endometriosis in a murine model either in the peritoneal cavity (proximal) or at a subcutaneous remote site (distal). The expression of several genes that are involved in endometrial receptivity (homeobox A10 [Hoxa10], homeobox A11 [Hoxa11], insulin-like growth factor binding protein 1 [Igfbp1], Kruppel-like factor 9 [Klf9], and progesterone receptor [Pgr]) was measured in the eutopic endometrium of mice transplanted with either proximal or distal endometriosis lesions. Decreased expression of Hoxa10, Igfbp1, Klf9, and total Pgr genes was observed in the eutopic endometrium of mice with peritoneal endometriosis. In the mice with distal lesions, overall expression of these genes was not as severely affected, however, Igfbp1 expression was similarly decreased and the effect on Pgr was more pronounced. Endometriosis does have a systemic effect that varies with distance to the end organ. However, even remote disease selectively and profoundly alters the expression of genes such as Pgr. This is the first controlled experiment demonstrating that endometriosis is not simply a local peritoneal disease. Selective alteration of genes critical for endometrial receptivity and endometriosis propagation may be systemic. Similarly, systemic effects of endometriosis on other organs may also be responsible for the widespread manifestations of the disease.

 

 

Taiwan J Obstet Gynecol. 2015 Oct;54(5):512-8.

Decreasing trend of hysterectomy in Taiwan: A population-based study, 1997-2010.

Lai JC¹, Huang N², Huang SM³, Hu HY⁴, Wang CW⁵, Chou YJ⁶, Wang KL⁷.

 

Abstract

OBJECTIVE:

Gynecologists in Taiwan are lacking a comprehensive picture of the changes in clinical practice and indications of hysterectomy over a long period of time. The aims of this study were to examine the national trends in the utilization of hysterectomy and to explore changes in its utilization rate over a 14-year period from 1997 to 2010.

MATERIALS AND METHODS:

We conducted a population-based trend analysis using the claims data from the Taiwan’s National Health Insurance program.

RESULTS:

We identified a total of 341,993 women aged 20 years or older who underwent hysterectomy between 1997 and 2010. The total number of hysterectomies increased from 22,961 in 1997 to 27,757 cases in 1999, followed by a decline to 22,351 in 2010. Overall, 5406 fewer hysterectomies (-19.5%) were performed in 2010 when compared with those performed in 1999. The number of hysterectomies performed decreased from 1997 to 2010 for precancerous lesions (-55.6%), chronic pelvic pain (-35.2%), uterine leiomyoma (-13.1%), and uterine prolapse (-7.2%). However, the utilization of hysterectomy increased for endometriosis (+76.3%) and gynecologic cancer (+22.7%) during the same time frame.

CONCLUSION:

The clinical utilization and primary indications of hysterectomy changed substantially in Taiwan from 1997 to 2010. The continued monitoring of changes in hysterectomy rates will be critical for understanding the appropriate indications for hysterectomy and oophorectomy, the emergence of alternative managements for uterine disorders, and future trends in women’s reproductive health.

 

 

Taiwan J Obstet Gynecol. 2015 Oct;54(5):559-66.

Detection of human papillomavirus in squamous cell carcinoma arising from dermoid cysts.

Chiang AJ¹, Chen DR², Cheng JT³, Chang TH⁴.

 

Abstract

OBJECTIVE:

Primary squamous cell carcinoma (SCC) of the ovary in humans is rare. Most cases represent a malignant transformation of ovarian teratoma, Brenner tumor, or endometriosis. The etiology of this cancer remains largely unknown. Human papillomavirus (HPV) infection is a critical factor that induces tumor formation, particularly cervical cancer. Therefore, this study aimed to evaluate the association of HPV with malignant transformation of mature cystic teratoma (MCT) into SCC of the ovary.

MATERIALS AND METHODS:

The samples included four formalin-fixed paraffin-embedded SCC-MCT tissues and their adjacent tissues from the cervix to the ovaries, 12 cases of benign teratoma ovarian tissues (dermoid tissues), and 11 cases of benign nonteratoma ovarian tissues (nondermoid tissues). The two squamous carcinoma tissues of the cervix were used as control samples. HPV was detected by immunohistochemistry (IHC) with anti-HPV capsid or E6 (HPV type 16/18) antibodies and in situ hybridization (ISH) with three sets of genotyping probes, HPV types 6/11, 16/18, and 31/33.

RESULTS:

IHC revealed HPV infection associated with the four cases of SCC-MCT and the two cases of control cervical cancer samples. Importantly, HPV was also detected in adjacent reproductive tissues of the SCC-MCT cases, which suggested that the viral particles might spread in an ascending route through the fallopian tubes, endometrium, endocervix, and cervix to the ovaries. ISH revealed HPV type 16/18 in all SCC-MCT cases and HPV type 31/33 in two, with no HPV type 6/11 in any SCC-MCT cases. However, compared with the SCC-MCT cases, the lower detection rates of HPV in dermoid cysts and nondermoid tissues suggested that HPV might not be associated with normal ovarian tissues or benign ovarian teratomas.

CONCLUSION:

Our data suggest that high-risk HPV infection might be a causal factor that induces malignant transformation of MCT into SCC of the ovary, although further investigation is still required.

 

 

Clin Exp Obstet Gynecol. 2015;42(5):671-2.

Resolution of pelvic pain related to adenomyosis following treatment with dextroamphetamine sulfate.

Check JH, Jaffe A.

 

Abstract

PURPOSE:

To determine if treatment with dextroamphetamine sulfate can reduce pelvic pain that was attributed to adenomyosis.

MATERIALS AND METHODS:

Dextroamphetamine sulfate was given to a 32-year-old woman who suffered on a daily basis from severe chronic pelvic pain that was not relieved by laparoscopic removal of endometriosis by oral contraceptive and ibuprofen. The adenomyosis was diagnosed by magnetic resonance imaging.

RESULTS:

Within three months the pain was completely gone and has remained absent for six months.

CONCLUSIONS:

Dextroamphetamine sulfate relieved pain from adenomyosis similar to its effect on endometriosis.

 

 

Arch Gynecol Obstet. 2016 May;293(5):1049-52

AMH trend after laparoscopic cystectomy and ovarian suturing in patients with endometriomas.

Shao MJ¹, Hu M², He YQ², Xu XJ².

 

Abstract

PURPOSE:

To evaluate the ovarian reserve after laparoscopic cystectomy with suturing in patients with endometriomas.

METHODS:

A total of 80 women with unilateral or bilateral endometriomas underwent laparoscopic cystectomy using sutures for hemostasis after the excision of ovarian cysts. Serum levels of antimullerian hormone (AMH) and FSH were measured at the day 3 of menstrual cycles preoperatively, 6 and 12 months postoperatively.

RESULTS:

In the bilateral endometrioma group, serum AMH level decreased significantly from the baseline (4.68 ± 2.87 ng/ml) to 6 months (3.05 ± 1.99 ng/ml) and 12 months (2.26 ± 1.88 ng/ml) postoperatively, whereas the FSH level increased significantly from baseline to 12 months postoperatively (P < 0.05). Those patients with unilateral endometriomas also had lower levels of AMH in 6 and 12 months after operation. When compared between unilateral and bilateral endometrioma group, the rate of AMH decline 6 and 12 months and the rate of FSH increase 12 months postoperatively reached statistical significance (P < 0.05).

CONCLUSIONS:

The changes of the AMH and FSH values suggest that the ovarian reserve is obviously reduced in spite of suturing technology used as a method of hemostasis after stripping ovarian endometriomas, especially in those with bilateral cysts. The protective effect of the ovarian suturing for ovarian reserve may be marginal.

 

 

Chest. 2015 Nov;148(5):e148-e151.

A 34-Year-Old Woman With Recurrent Right-Sided Chest Pain and Dyspnea.

Albores J¹, Fishbein G², Bando J³.

 

Abstract

A 34-year-old woman presented with her third episode of acute-onset right-sided chest pain and dyspnea. She had two prior similar occurrences of right-sided sharp, pleuritic chest pain with radiation to the back and dyspnea. Chest radiographs during these presentations revealed a small apical right-sided pneumothorax that was managed conservatively with high-flow oxygen. All three presentations were associated with vigorous exercise and the first day of her menses. She denied cough, hemoptysis, fever, smoking history, airplane travel, scuba diving, or trauma during these presentations. The patient has been trying to conceive for the past year but has been unsuccessful because of uterine fibroids but no history of endometriosis.

 

 

J Obstet Gynaecol Res. 2015 Dec;41(12):1927-34.

Liver receptor homologue-1 and steroidogenic factor-1 expression in cultured granulosa cells from patients with endometriosis: A preliminary study.

Lu X¹, Wu ZM¹, Wang YW¹, Wang M¹, Cheng WW¹.

 

Abstract

AIM:

The expression of aromatase (via CYP19 and the CYP19 PII promoter) and the orphan nuclear receptor family members, liver receptor homologue-1 (LRH-1) and steroidogenic factor-1 (SF-1) in cultured luteinized granulosa cells from women with endometriosis were investigated.

METHODS:

Luteinized granulosa cells from patients undergoing in vitro fertilization (16 patients with endometriosis and 28 controls) were examined for messenger ribonucleic acid (mRNA) expression of CYP19, CYP19 PII, LRH-1 and SF-1, determined by quantitative reverse transcription-polymerase chain reaction. Student’s t-test, the Mann-Whitney U test and Spearman’s rank correlation were used for statistical analysis.

RESULTS:

The number of high quality embryos in the endometriosis group was significantly lower than in the control group. The mRNA expression levels of CYP19, CYP19 PII, LRH-1 and SF-1 in granulosa-lutein cells were decreased in women with endometriosis compared to the control group. The simultaneous down-regulation expression of LRH-1, SF-1 and CYP19 PII in endometriotic granulosa cells indicated their positive correlation.

CONCLUSION:

Our results demonstrate aberrant expressions of SF-1 and LRH-1 in endometriotic granulosa-lutein cells. This finding may be helpful in understanding infertility associated with endometriosis and reduced P450 aromatase activity in endometriotic granulosa cells.

 

 

 

J Obstet Gynaecol Res. 2016 Feb;42(2):217-23.

Clear cell adenocarcinoma arising from adenomyotic cyst: A case report and literature review.

Baba A¹, Yamazoe S¹, Dogru M¹, Ogawa M², Takamatsu K², Miyauchi J³.

 

Abstract

Ovaries are the primary sites of cancerous disease that is derived from endometriosis. Uterine cancer originating from endometriosis is very rare. The most frequent histological subtype of cancer derived from endometriosis is endometrioid adenocarcinoma, a subtype of clear cell carcinoma which is exceedingly rare. We report a case of a 40-year-old Japanese woman with a six year history of uterine leiomyoma. The patient was clinically and radiologically suspected to have degenerative uterine myoma with a possible malignant association and underwent a transabdominal total hysterectomy. Histopathological examination of the specimens revealed clear cell adenocarcinoma arising from the adenomyotic cyst. A literature review of clear cell adenocarcinomas arising from uterine adenomyotic cysts (cystic adenomyosis), emphasizes the clinically and radiologically important features of this very rare entity. Clear cell carcinoma association should be suspected in patients who are under follow-up for uterine myomas and present with cystic uterine changes with solid component on magnetic resonance imaging or computed tomography scans.

 

 

J Robot Surg. 2015 Sep;9(3):211-3.

Concurrent use of a robotic uterine manipulator and a robotic laparoscope holder to achieve assistant-less solo laparoscopy: the double ViKY.

Maheshwari M¹, Ind T^2,3.

 

Abstract

Three patients requiring gynecological surgery had uterine manipulation using a VCare(®) controlled by a ViKY(®) at the same time as having a ViKY(®) robotic arm controlling the laparoscope. The setup time for each varied from 6-9 min for the uterine manipulator and 3-5 min for the laparoscope holder. In all cases (one endometriosis and two dermoid cysts) the operative field was good. Two patients were discharged within 24 h of surgery. One patient required an extra day in hospital after she went into acute urinary retention once the catheter was removed. This work demonstrated that assistant-less solo gynecological surgery is feasible using two ViKY robotic arms for both uterine manipulation and laparoscope holding.

 

 

Chirurgia (Bucur). 2015 Sep-Oct;110(5):482-5.

Accurate Diagnosis of Sigmoid Colon Endometriosis by Immunohistochemistry and Transmission Electron Microscopy – A Case Report.

Constantin V, Carăp A, Bobic S, Pâun I, Brâtilâ E, Socea B, Moroşanu AM, Mirancea N.

 

Abstract

Endometriosis is described as the presence of functioning endometrial tissue at sites outside the uterus. Up to 15% ofwomen in their reproductive period are affected by this condition. Endometriosis is mostly foundon the uterosacral ligaments, inside the rectovaginalseptum or vagina, in the rectosigmoid area, ovarianfossa, pelvic peritoneum, ureters, and bladder, causinga distortion of the pelvic anatomy. Colonic involvement is rare but is usually found at the level of the rectum or the sigmoid colon. Acute presentation with intestinal obstruction or perforation is rare. While malignant transformation of endometrial lesions is rare, findings of dysplasia on pathology sections can give rise to questions of management. Immunohistochemistry and electron microscopy can help decision making. We present the case of a 38 year old woman with intestinal obstruction caused by sigmoid colon endometriosis with moderate dysplasia in which transmission electron microscopy was used for postoperative diagnosis. Detailed analysis of these cases, while logistically difficult, can prove useful in understanding the etiology and pathophysiology of the disease.

 

 

J Midlife Health. 2015 Jul-Sep;6(3):122-4.

Endometriosis presenting as carcinoma colon in a perimenopausal woman.

Muthyala T¹, Sikka P¹, Aggarwal N¹, Suri V¹, Gupta R², Nahar U³.

 

Abstract

Endometriosis is a common benign disease of reproductive age women, and can involve the intestinal tract. Inconsistent clinical presentation, similar features on radiological imaging and colonoscopy with other inflammatory and malignant lesions of the bowel makes the preoperative diagnosis of bowel endometriosisdifficult. We present a case of a 42-year-old perimenopausal female clinically presented, investigated and managed in the lines of carcinoma of sigmoid colon. She underwent terminal ileac resection with end to end anastomoses, Hartmann’s procedure and total hysterectomy with bilateral salpingoophorectomy. The histopathological report revealed endometriosis of small intestine, large intestine, mesentery, right ovary and adenomyoma of uterus. Thus, bowel endometriosis should also be considered as differential diagnosis in reproductive age women with gastrointestinal symptoms or intestinal mass of uncertain diagnosis.

 

Acta Radiol. 2016 Aug;57(8):998-1005.

Diffusion-weighted magnetic resonance imaging in the differentiation of endometriomas from hemorrhagic cysts in the ovary.

Lee NK¹, Kim S², Kim KH³, Suh DS³, Kim TU⁴, Han GJ¹, Lee JW¹, Kim JY¹.

 

Abstract

BACKGROUND:

The classic magnetic resonance imaging (MRI) feature of endometriomas is the shading sign, which is characterized by T2-shortening in ovarian cystic lesions that are hyperintense on T1-weighted images. The shading sign is infrequently observed in hemorrhagic ovarian cysts.

PURPOSE:

To investigate the value of MRI with diffusion-weighted imaging (DWI) for distinguishing endometriomas from hemorrhagic cysts in the ovary.

MATERIAL AND METHODS:

This retrospective study included 91 patients with 98 ovarian endometriomas and 21 hemorrhagic ovarian cysts that were confirmed pathologically, who had undergone MRI with DWI. Two radiologists compared MRI features, including size, bilaterality, multilocularity, the shading sign, the ovarian lesion/muscle signal intensity ratio at T2-weighted images, and T2 dark spots, between endometriomas and hemorrhagic cysts. We also compared the mean ADC value between endometriomas and hemorrhagic cysts, and determined the optimal cutoff ADC value for differentiating endometriomas from hemorrhagic cysts.

RESULTS:

The size and mean ADC values were significantly different between endometriomas and hemorrhagic cysts. The mean ADC values of endometriomas and hemorrhagic cysts were 1.06 ± 0.38 × 10 (-3) mm(2)/s and 0.73 ± 0.29 × 10(-3) mm(2)/s, respectively (P < 0.002). The optimal cutoff ADC value for differentiating endometriomas from hemorrhagic cysts was 0.849 × 10(-3) mm(2)/s (sensitivity, 77.6%; specificity, 76.2%).

CONCLUSION:

The addition of DWI could help in differentiating endometriomas from hemorrhagic cysts in the ovary, when conventional MRI is challenging.

 

 

 

 

 

J Affect Disord. 2016 Jan 15;190:282-285.

Risk of developing major depression and anxiety disorders among women with endometriosis: A longitudinal follow-up study.

Chen LC¹, Hsu JW², Huang KL², Bai YM², Su TP², Li CT², Yang AC², Chang WH¹, Chen TJ³, Tsai SJ⁴, Chen MH⁵.

 

Abstract

BACKGROUNDS:

Several cross-sectional studies suggested a link between endometriosis and mood disorders. However, the temporal association between endometriosis and mood disorders (depression and anxiety disorders) is still unclear.

METHODS:

Using the Taiwan National Health Insurance Research Database, 10,439 women with endometriosisand 10,439 (1:1) age-/sex-matched controls between 1998 and 2009 were enrolled, and followed up to the end of 2011. Those who developed depression or anxiety disorders during the follow-up were identified.

RESULTS:

Women with endometriosis had an increased risk of developing major depression (hazard ratio [HR]: 1.56, 95% confidence interval [CI]:1.24-1.97), any depressive disorder (HR: 1.44, 95% CI: 1.25-1.65), and anxiety disorders (HR: 1.44, 95% CI: 1.22-1.70) in later life compared to those without endometriosis. Stratified by age group, women with endometriosis aged <40 years and those aged ≧40 years were both prone to developing major depression (HR: 1.52, 95% CI: 1.15-1.99; HR: 1.69, 95% CI: 1.09-2.62), any depressive disorder (HR: 1.43, 95% CI: 1.21-1.69; HR: 1.45, 95% CI: 1.13-1.56), and anxiety disorders (HR: 1.39, 95% CI: 1.14-1.71; HR: 1.53, 95% CI: 1.15-2.04).

LIMITATION:

the incidence of depression and anxiety disorders may be underestimated since only those who sought medical consultation and help would be enrolled in our study.

CONCLUSION:

Endometriosis was associated with an elevated likelihood of developing depression and anxiety disorders. Further studies may be required to investigate the underlying pathophysiology between endometriosisand both depression and anxiety disorders.

 

 

 

 

Cell. 2015 Nov 5;163(4):960-74.

Estrogen Receptor β Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis.

Han SJ¹, Jung SY², Wu SP¹, Hawkins SM³, Park MJ¹, Kyo S⁴, Qin J², Lydon JP¹, Tsai SY¹, Tsai MJ¹, DeMayo FJ¹, O’Malley BW⁵.

 

Abstract

Alterations in estrogen-mediated cellular signaling play an essential role in the pathogenesis of endometriosis. In addition to higher estrogen receptor (ER) β levels, enhanced ERβ activity was detected in endometriotic tissues, and the inhibition of enhanced ERβ activity by an ERβ-selective antagonist suppressed mouse ectopic lesion growth. Notably, gain of ERβ function stimulated the progression of endometriosis. As a mechanism to evade endogenous immune surveillance for cell survival, ERβ interacts with cellular apoptotic machinery in the cytoplasm to inhibit TNF-α-induced apoptosis. ERβ also interacts with components of the cytoplasmic inflammasome to increase interleukin-1β and thus enhance its cellular adhesion and proliferation properties. Furthermore, this gain of ERβ function enhances epithelial-mesenchymal transition signaling, thereby increasing the invasion activity of endometriotic tissues for establishment of ectopic lesions. Collectively, we reveal how endometrial tissue generated by retrograde menstruation can escape immune surveillance and develop into sustained ectopic lesions via gain of ERβ function.

 

 

Eur J Obstet Gynecol Reprod Biol. 2015 Dec;195:156-9.

The impact of GnRH agonists in patients with endometriosis on prolactin and sex hormone levels: a pilot study.

Marschalek J¹, Ott J¹, Husslein H¹, Kuessel L¹, Elhenicky M¹, Mayerhofer K¹, Franz MB².

 

Abstract

OBJECTIVE:

Gonadotropin releasing hormone agonists (GnRHa) decrease the expression of growth factors involved in the development of human endometriotic tissue. As endometriosis has been found to be associated with a mild increase in prolactin (PRL) serum levels, we aimed to evaluate changes in PRL serum levels as well as other hormones relevant to endometriosis and infertility during long-term administration of GnRHas in women with endometriosis.

STUDY DESIGN:

In this prospective pilot study we obtained blood samples on the first day of leuporeline administration and then subsequently after 4, 8 and 12 weeks in 22 patients.

RESULTS:

Median PRL levels were unchanged after 4 weeks, but significantly decreased 8 and 12 weeks after the first leuporeline administration (p1=0.085, p2=0.020, p3=0.001). There was no significant decrease in serum anti-Mullerian hormone (AMH) levels over the whole period of down regulation with leuporeline (p1-3>0.05).

CONCLUSION:

Our data support the hypothesis that the decrease of PRL levels might contribute to the known effect of GnRH treatment in patients with endometriosis via suppression of VEGF expression in endometriotic lesions. Moreover this study lends support to the thesis that AMH remains stable under GnRHa therapy and therefore can be also used as a marker of ovarian function prior to IVF-stimulation during down regulation.

 

 

J Ultrasound. 2014 Jun 13;18(4):411-4.

A rare case of sigmoid colon obstruction in patient with ulcerative colitis: role of transabdominal ultrasound-guided biopsy.

Terracciano F¹, Scalisi G², Attino V³, Biscaglia G¹.

 

Abstract

in English, Italian

INTRODUCTION:

Endometriosis is a common chronic gynaecological disease affecting 10 % of women of reproductive age. Of these 5-12 % may present bowel endometriosis that may be asymptomatic or associated with aspecific symptoms even bowel obstruction.

CASE PRESENTATION:

The case of a 41-year-old woman with history of ulcerative colitis, previous diagnosis of ovarian endometriosis, recurrent abdominal pain not related to the menstrual cycle, with abdominal pain and obstinate constipation for 2 weeks was referred. The patient underwent colonoscopy, transabdominal ultrasound and ultrasound-guided fine-needle biopsy to have a diagnosis.

DISCUSSION:

Endometriosis should be considered in the differential diagnosis of every woman of childbearing age who presents with gastrointestinal or abdominal symptoms. As demonstrated in our case and by the burgeoning literature in this field, we believe that the role of transabdominal ultrasound should be reconsidered in the management of abdominal diseases because this examination associated with ultrasound-guided fine-needle biopsy allows, in expert hands, to obtain adequate histological samples avoiding patients to undergo more invasive tests to get a diagnosis.

 

 

Int J Clin Exp Med. 2015 Aug 15;8(8):14085-9.

Traditional Chinese medical herbs staged therapy in infertile women with endometriosis: a clinical study.

Ding Z¹, Lian F².

 

Abstract

BACKGROUND:

Endometriosis is a common gynecological disease defined as the presence of endometrioid tissue (glands and stroma) outside the uterus. About 30 to 40% patients with endometriosis are infertile. In traditional Chinese medical system, endometriosis associated infertility is mostly caused by kidney deficiency and blood stasis. The herb of reinforcing kidney and removing blood stasis is designed to treat the disease.

MATERIAL AND METHODS:

All the 80 up-to-standard patients were divided into two different groups exactly according to the random principle. They were treated with hormone and traditional Chinese medical herb separately. After half year’s therapy, all the patients received one year’s follow-up. Their transvaginal ultrasonographic changes, serum hormone levels and pregnancy rate were recorded to analysis the effect.

RESULTS:

No significant difference happened in two groups’ demographic and clinical characteristics (P > 0.05). After the treatment, the effect on serum hormone levels and specific markers are significant (P < 0.05). The transvaginal ultrasonographic changes were positive, too. The text on hepatic and renal function confirmed to the safety of the herb. Compared to hormone therapy, the traditional Chinese medical herb is safe and effective for endometriosis patients with infertility.

CONCLUSION:

Compared with hormone therapy, traditional Chinese medical herb’s two-staged therapy is effective and safe for endometriosis patients with infertility.

 

 

 

 

Int J Inflam. 2015;2015:452095

Curbing Inflammation in Multiple Sclerosis and Endometriosis: Should Mast Cells Be Targeted?

Hart DA¹.

 

Abstract

Inflammatory diseases and conditions can arise due to responses to a variety of external and internal stimuli. They can occur acutely in response to some stimuli and then become chronic leading to tissue damage and loss of function. While a number of cell types can be involved, mast cells are often present and can be involved in the acute and chronic processes. Recent studies in porcine and rabbit models have supported the concept of a central role for mast cells in a “nerve-mast cell-myofibroblast axis” in some inflammatory processes leading to fibrogenic outcomes. The current review is focused on the potential of extending aspects of this paradigm into treatments for multiple sclerosis and endometriosis, diseases not usually thought of as having common features, but both are reported to have activation of mast cells involved in their respective disease processes. Based on the discussion, it is proposed that targeting mast cells in these diseases, particularly the early phases, may be a fruitful avenue to control the recurring inflammatory exacerbations of the conditions.

 

 

Am J Surg Pathol. 2016 Mar;40(3):302-12.

Morphological and Immunohistochemical Reevaluation of Tumors Initially Diagnosed as Ovarian Endometrioid Carcinoma With Emphasis on High-grade Tumors.

Lim D¹, Murali R, Murray MP, Veras E, Park KJ, Soslow RA.

 

Abstract

Ovarian endometrioid carcinomas (OEC) of low grade have characteristic morphologic features, but high-grade tumors can mimic high-grade serous and undifferentiated carcinomas. We reviewed tumors initially diagnosed as OEC to determine whether a combination of pathologic and immunohistochemical features can improve histologic subclassification. Tumors initially diagnosed as OEC were reviewed using World Health Organization criteria. We also noted the presence of associated confirmatory endometrioid features (CEFs): (i) squamous metaplasia; (ii) endometriosis; (iii) adenofibromatous background; and (iv) borderline endometrioid or mixed Mullerian component. A tissue microarray was constructed from 27 representative tumors with CEF and 14 without CEF, and sections were stained for WT-1, p16, and p53. Of 109 tumors initially diagnosed as OEC, 76 (70%) tumors were classified as OEC. The median patient age was 55 years, and 75% of patients were younger than 60 years. Ninety-two percent presented with disease confined to the pelvis, and 87% of tumors were unilateral. The median tumor size was 11.8 cm. Only 3% of tumors were high grade (grade 3of 3). Eighty percent of cases had at least 1 CEF, and 59% had at least 2 CEFs. Eleven percent overexpressed p16, 0% overexpressed p53, and 3% expressed WT-1. Only 10% of patients died of disease at last follow-up. Thirty-three (33) tumors, or 30% of tumors originally classified as endometrioid, were reclassified as serous carcinoma (OSC). The median patient age was 54.5 years, and 59% of patients were younger than 60 years of age. Only 27% had disease confined to the pelvis at presentation, 52% of tumors were unilateral, and the median tumor size was 8 cm. Associated squamous differentiation, endometrioid adenofibroma, and endometrioid or mixed Mullerian borderline tumor (CEFs) were not present in any case, but 6% of patients had endometriosis. Approximately one half of the reclassified OSC demonstrated SET-pattern morphology (combinations of glandular, cribriform, solid, and transitional cell-like architecture) and were immunophenotypically indistinguishable from OSCs with papillary architecture. Sixty percent of OSC overexpressed p16, 50% overexpressed p53, and 82% expressed WT-1. At last follow-up, 52% had died of disease. Compared with OSC, OEC patients more frequently presented below 60 years of age (P=0.046), had low-stage tumors (P<0.001), were more frequently unilateral (P<0.001), more frequently had synchronous endometrial endometrioid carcinomas (P<0.001); and had no evidence of disease at last follow-up (P<0.001). Their tumors were of lower grade (P<0.001), had more CEFs (P<0.001), and less frequently overexpressed p16 and p53 (P=0.003 and P<0.001, respectively) and less frequently expressed WT-1 (P<0.001). This analysis emphasizes the diagnostic value of CEFs, the presence of a low-grade gland-forming endometrioid component, and WT-1 negativity, as valid, clinically relevant criteria for a diagnosis of OEC. Glandular and/or cribriform architecture alone may be seen in both OECs and OSCs and are therefore not informative of diagnosis. Further study is needed to elaborate the characteristics of the exceedingly rare high-grade OEC.

 

 

Cold Spring Harb Perspect Med. 2015 Nov 9;6

The Role of Hox Genes in Female Reproductive Tract Development, Adult Function, and Fertility.

Du H¹, Taylor HS¹.

 

Abstract

HOX genes convey positional identity that leads to the proper partitioning and adult identity of the female reproductive track. Abnormalities in reproductive tract development can be caused by HOX gene mutations or altered HOX gene expression. Diethylstilbestrol (DES) and other endocrine disruptors cause Müllerian defects by changing HOX gene expression. HOX genes are also essential regulators of adult endometrial development. Regulated HOXA10 and HOXA11 expression is necessary for endometrial receptivity; decreased HOXA10 or HOXA11 expression leads to decreased implantation rates. Alternation of HOXA10 and HOXA11 expression has been identified as a mechanism of the decreased implantation associated with endometriosis, polycystic ovarian syndrome, leiomyoma, polyps, adenomyosis, and hydrosalpinx. Alteration of HOX gene expression causes both uterine developmental abnormalities and impaired adult endometrial development that prevent implantation and lead to female infertility.

 

 

Hum Reprod Update. 2016 Mar-Apr;22(2):137-63.

Endometrial stem/progenitor cells: the first 10 years.

Gargett CE¹, Schwab KE², Deane JA³.

 

Abstract

BACKGROUND:

The existence of stem/progenitor cells in the endometrium was postulated many years ago, but the first functional evidence was only published in 2004. The identification of rare epithelial and stromal populations of clonogenic cells in human endometrium has opened an active area of research on endometrial stem/progenitor cells in the subsequent 10 years.

METHODS:

The published literature was searched using the PubMed database with the search terms ‘endometrial stem cells and menstrual blood stem cells’ until December 2014.

RESULTS:

Endometrial epithelial stem/progenitor cells have been identified as clonogenic cells in human and as label-retaining or CD44(+) cells in mouse endometrium, but their characterization has been modest. In contrast, endometrial mesenchymal stem/stromal cells (MSCs) have been well characterized and show similar properties to bone marrow MSCs. Specific markers for their enrichment have been identified, CD146(+)PDGFRβ(+) (platelet-derived growth factor receptor beta) and SUSD2(+) (sushi domain containing-2), which detected their perivascular location and likely pericyte identity in endometrial basalis and functionalis vessels. Transcriptomics and secretomics of SUSD2(+) cells confirm their perivascular phenotype. Stromal fibroblasts cultured from endometrial tissue or menstrual blood also have some MSC characteristics and demonstrate broad multilineage differentiation potential for mesodermal, endodermal and ectodermal lineages, indicating their plasticity. Side population (SP) cells are a mixed population, although predominantly vascular cells, which exhibit adult stem cell properties, including tissue reconstitution. There is some evidence that bone marrow cells contribute a small population of endometrial epithelial and stromal cells. The discovery of specific markers for endometrial stem/progenitor cells has enabled the examination of their role in endometrial proliferative disorders, including endometriosis, adenomyosis and Asherman’s syndrome. Endometrial MSCs (eMSCs) and menstrual blood stromal fibroblasts are an attractive source of MSCs for regenerative medicine because of their relative ease of acquisition with minimal morbidity. Their homologous and non-homologous use as autologous and allogeneic cells for therapeutic purposes is currently being assessed in preclinical animal models of pelvic organ prolapse and phase I/II clinical trials for cardiac failure. eMSCs and stromal fibroblasts also exhibit non-stem cell-associated immunomodulatory and anti-inflammatory properties, further emphasizing their desirable properties for cell-based therapies.

CONCLUSIONS:

Much has been learnt about endometrial stem/progenitor cells in the 10 years since their discovery, although several unresolved issues remain. These include rationalizing the terminology and diagnostic characteristics used for distinguishing perivascular stem/progenitor cells from stromal fibroblasts, which also have considerable differentiation potential. The hierarchical relationship between clonogenic epithelial progenitor cells, endometrial and decidual SP cells, CD146(+)PDGFR-β(+) and SUSD2(+) cells and menstrual blood stromal fibroblasts still needs to be resolved. Developing more genetic animal models for investigating the role of endometrial stem/progenitor cells in endometrial disorders is required, as well as elucidating which bone marrow cells contribute to endometrial tissue. Deep sequencing and epigenetic profiling of enriched populations of endometrial stem/progenitor cells and their differentiated progeny at the population and single-cell level will shed new light on the regulation and function of endometrial stem/progenitor cells.

 

 

Expert Opin Ther Targets. 2016;20(5):593-600.

Challenges in the development of novel therapeutic strategies for treatment of endometriosis.

Vanhie A¹, Tomassetti C¹, Peeraer K¹, Meuleman C^1,2, D’Hooghe T².

 

Abstract

INTRODUCTION:

Endometriosis is an estrogen-dependent disease that results in pelvic pain and infertility. Its treatment is often frustrating due to limited medical treatment options, complex surgical treatment and high recurrence rates. Despite the advances in our understanding of the pathogenesis over the last decades and the consequent novel therapeutic strategies, no new drugs have been introduced in daily clinical practice.

AREAS COVERED:

In the first part we present an overview of the pathogenesis of endometriosis. In the second part we discuss how new insights have led to the development of novel nonhormonal strategies for the treatment of endometriosis, focusing on anti-inflammatory and anti-angiogenic agents. In the third part we describe the problems encountered in the translation from experimental drugs to routine medicine for the treatment of endometriosis.

EXPERT OPINION:

Despite the multitude of agents that have been tested in preclinical trials, only few drugs have passed to the stage of clinical testing and none have been introduced into clinical practice. It is our opinion that the major challenges in the translation from novel agents for endometriosis is due to the use of inadequate rodent models and a lack of standardization in the design and reporting of preclinical endometriosis models.