Medicine (Baltimore). 2016 Oct;95(40):e4957.

Physical activity and endometriosis risk in women with infertility or pain: Systematic review and meta-analysis.

Ricci E¹, Viganò P, Cipriani S, Chiaffarino F, Bianchi S, Rebonato G, Parazzini F.

 

Abstract

BACKGROUND:

The potential association between endometriosis and physical activity (PA) has been suggested in several epidemiological studies.We aimed to establish whether PA influences endometriosis risk.

METHODS:

MEDLINE and EMBASE were searched using “physical activity” OR “exercise” combined with “endometriosis,” in Medical Subject Headings and free text. We selected original articles in English, published up to April 2016, evaluating the association between endometriosis and recent or past PA (case-control or cohort studies). References of retrieved papers were reviewed. We computed summary odds ratios (ORs) of endometriosis for recent and past PA.

RESULTS:

Six case-control and 3 cohort studies included 3355 cases for recent PA and 4600 cases for past PA. The summary OR for endometriosis according to PA level, calculated by the random-effect model, was 0.85 [95% confidence interval (CI) 0.67-1.07] for any recent versus no PA. As compared to no recent PA, ORs for low and moderate/high PA were 1.00 (95% CI: 0.68-1.28) and 0.75 (95% CI: 0.53-1.07), respectively.

CONCLUSIONS:

Though it suggests that PA may reduce the risk of endometriosis, this meta-analysis does not conclusively support the hypothesis. Whether our findings are really explained by the benefit of exercise at molecular and endocrine level, or related to confounding mechanisms, such as study design, choice of controls, and PA potentially improving pain, needs to be further investigated.

 

 

Pain. 2016 Nov;157(11):2571-2581.

Genome-wide association analysis of pain severity in dysmenorrhea identifies association at chromosome 1p13.2, near the nerve growth factor locus.

Jones AV¹, Hockley JR, Hyde C, Gorman D, Sredic-Rhodes A, Bilsland J, McMurray G, Furlotte NA, Hu Y, Hinds DA, Cox PJ, Scollen S.

 

Abstract

Dysmenorrhea is a common chronic pelvic pain syndrome affecting women of childbearing potential. Family studies suggest that genetic background influences the severity of dysmenorrhea, but genetic predisposition and molecular mechanisms underlying dysmenorrhea are not understood. In this study, we conduct the first genome-wide association study to identify genetic factors associated with dysmenorrhea pain severity. A cohort of females of European descent (n = 11,891) aged 18 to 45 years rated their average dysmenorrhea pain severity. We used a linear regression model adjusting for age and body mass index, identifying one genome-wide significant (P < 5 × 10) association (rs7523086, P = 4.1 × 10, effect size 0.1 [95% confidence interval, 0.074-0.126]). This single nucleotide polymorphism is colocalising with NGF, encoding nerve growth factor. The presence of one risk allele corresponds to a predicted 0.1-point increase in pain intensity on a 4-point ordinal pain scale. The putative effects on NGF function and/or expression remain unknown. However, genetic variation colocalises with active epigenetic marks in fat and ovary tissues, and expression levels in aorta tissue of a noncoding RNA flanking NGF correlate. Participants reporting extreme dysmenorrhea pain were more likely to report being positive for endometriosis, polycystic ovarian syndrome, depression, and other psychiatric disorders. Our results indicate that dysmenorrhea pain severity is partly genetically determined. NGF already has an established role in chronic pain disorders, and our findings suggest that NGF may be an important mediator for gynaecological/pelvic pain in the viscera.

 

 

Clin Genet. 2017 Feb;91(2):254-264.

Recent insights on the genetics and epigenetics of endometriosis.

Borghese B^1,2, Zondervan KT³, Abrao MS^4,5, Chapron C^1,2, Vaiman D^1,2.

 

Abstract

Endometriosis is a gynecologic disease affecting up to 10% of the women and a major cause of pain and infertility. It is characterized by the implantation of functional endometrial tissue at ectopic positions generally within the peritoneum. This complex disease has an important genetic component with a heritability estimated at around 50%. This review aims at providing recent insights into the genetic bases of endometriosis, and presents a detailed overview of evidence of epigenetic alterations specific to this disease. In the future, these alterations may constitute therapeutic targets for pharmacological compounds able to modify the epigenetic code.

 

 

 

 

J Endocrinol Invest. 2016 Nov;39(11):1259-1265.

Fertility in women of late reproductive age: the role of serum anti-Müllerian hormone (AMH) levels in its assessment.

Meczekalski B¹, Czyzyk A², Kunicki M³, Podfigurna-Stopa A², Plociennik L³, Jakiel G^4,5, Maciejewska-Jeske M², Lukaszuk K^3,4,6.

 

Abstract

INTRODUCTION:

Fertility is referred to the capability for having offspring and can be evaluated by fertility rate. Women’s fertility is strictly dependent on individual’s age. The fertility peak occurs in the early 20s, and it starts to decline in the third and fourth decades of life (falling sharply after age 35).

AIM:

The aim of this work is to review the available data concerning fertility in women of late reproductive age, especially the role of serum anti-Müllerian hormone (AMH) levels.

RESULTS:

There are a lot of factors responsible for decrease of fertility in women of late reproductive age. These factors can be classified as oocyte-dependent (decrease in oocyte quantity and quality) and oocyte-independent (reproductive organs [uterus, oviducts] status and general health). Anti-Müllerian hormone (AMH) is a dimeric glycoprotein of the transforming growth factor-β (TGF-β) superfamily produced directly by the ovarian granulosa cells of secondary, preantral, and early antral follicles. It has been used as an ovarian reserve marker since 2002. Anti-Müllerian hormone seems to be the best endocrine marker for assessing the age-related decline of the ovarian pool in healthy women. Evaluation of AMH’s predictive value in the naturally aging population is important for counseling women about reproductive planning as well as for treatment planning for women experiencing hormone-sensitive gynecological conditions such as endometriosis and fibroids.

CONCLUSIONS:

AMH can be considered as an indicator of fertility in late reproductive age women and pregnancy outcome in assisted reproductive technology cycles. AMH can strongly predict poor response in the controlled ovarian stimulation.

 

 

Proteins. 2016 Nov;84(11):1625-1643.

Structural mutation analysis of PTEN and its genotype-phenotype correlations in endometriosis and cancer.

Smith IN¹, Briggs JM².

 

Abstract

The phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene encodes a tumor suppressor phosphatase that has recently been found to be frequently mutated in patients with endometriosis, endometrial cancer and ovarian cancer. Here, we present the first computational analysis of 13 somatic missense PTEN mutations associated with these phenotypes. We found that a majority of the mutations are associated in conserved positions within the active site and are clustered within the signature motif, which contain residues that play a crucial role in loop conformation and are essential for catalysis. In silico analyses were utilized to identify the putative effects of these mutations. In addition, coarse-grained models of both wild-type (WT) PTEN and mutants were constructed using elastic network models to explore the interplay of the structural and global dynamic effects that the mutations have on the relationship between genotype and phenotype. The effects of the mutations reveal that the local structure and interactions affect polarity, protein structure stability, electrostatic surface potential, and global dynamics of the protein. Our results offer new insight into the role in which PTEN missense mutations contribute to the molecular mechanism and genotypic-phenotypic correlation of endometriosis, endometrial cancer, and ovarian cancer. Proteins 2016; 84:1625-1643. © 2016 Wiley Periodicals, Inc.

 

 

Arch Gynecol Obstet. 2016 Nov;294(6):1257-1263.

Gonadotropin-releasing hormone agonist with add-back treatment is as effective and tolerable as dienogest in preventing pain recurrence after laparoscopic surgery for endometriosis.

Lee DY¹, Lee JY¹, Seo JW¹, Yoon BK¹, Choi D².

 

Abstract

PURPOSE:

This study was performed to compare the efficacy and tolerability of GnRH agonist with add-back therapy versus dienogest treatment for preventing pelvic pain recurrence after laparoscopic surgery for endometriosis.

METHODS:

Sixty-four reproductive-aged women who underwent laparoscopic surgery for endometriosis received post-operative medical treatment with either GnRH agonist plus 17β-estradiol and norethisterone acetate (n = 28) or dienogest (n = 36) for 6 months. The pre- to post-treatment changes in pain were assessed using a visual analogue scale, and changes in quality-of-life and menopausal symptoms were measured by questionnaire.

RESULTS:

Visual analogue scale pain score decreased significantly for both treatments with no significant differences between groups. Neither physical, psychological, social, and environmental components of quality-of-life nor menopausal rating scale score were significantly different between the two groups. Bone mineral density at the lumbar spine declined significantly in both treatment groups (-2.5 % for GnRH agonist plus add-back and -2.3 % for dienogest), with no significant difference between the two groups.

CONCLUSION:

GnRH agonist and add-back therapy using 17β-estradiol and norethisterone acetate are as effective and tolerable as dienogest for the prevention of pelvic pain recurrence after laparoscopic surgery for endometriosis.

 

 

Gynecol Endocrinol. 2016 Oct;32(sup2):75-79.

Innovative approach in assessing the role of neurogenesis, angiogenesis, and lymphangiogenesis in the pathogenesis of external genital endometriosis.

Sheveleva T¹, Bejenar V², Komlichenko E², Dedul A^2,3, Malushko A⁴.

 

Abstract

Endometriosis is a chronic, progressive, relapsing estrogen-dependent disorder characterized by the growth of tissue structure and function similar to the endometrium outside the normal mucosa of the uterine cavity localization. Endometriosis is found in 10-15% of women in reproductive age and it is one of the main causes of pelvic pain syndrome and infertility. Mechanisms of the development of endometriosis and related pathological pain impulses are still poorly understood and therapeutic approaches do not always have a sufficient effect; in this connection, the study of the pathogenesis of endometriosis and endometriosis-associated pain currently is perspective. Identification of significant factors of angiogenesis, lymphangiogenesis, and neurogenesis in the external genital endometriosis will promote the development of non-invasive early diagnosis and pathogenetic therapy.

 

 

Gynecol Endocrinol. 2016 Oct;32(sup2):33-36.

Immunohistochemical criteria for endometrial receptivity in I/II stage endometriosis IVF-treated patients.

Krylova Y¹, Polyakova V¹, Kvetnoy I¹, Kogan I², Dzhemlikhanova L^2,3, Niauri D³, Gzgzyan A^2,3, Ailamazyan E^2,3.

 

Abstract

Abstracts Background: Implantation failure of in vitro fertilization (IVF) cycles is recognized as one of key problems in contemporary reproductive medicine. Implantation itself is a multifactorial process and one can hardly expect to find a single criterion for the endometrium receptivity. Endometrium biopsy still remains the most applicable technique to diagnose abnormalities causing decrease or complete loss of endometrial receptivity.

MATERIALS AND METHODS:

We have studied 95 endometrial biopsy samples from 45 patient with I/II stage endometriosis and 40 controls from October 2014 to December 2015. Immunohistochemical analysis of key biological molecules participating in implant window formation (LIF, ER, PR, integrin, TGF-β1 and VEGF) was done to assess their predicting value for endometrial receptivity troubles.

RESULTS:

The discriminant analysis demonstrated that highest information capacity was characteristic for LIF expression percent area, integrin αVβ3 both percent area and optic density in endometrial stroma and glands and finally TGFβ1 and VEGF-А percent area expression in endometrial stroma. The model test done on a checking group showed 89.1% correct discrimination. Cross-checking in a teaching group showed a bit lower but still high correct answer percentage (88.8%). A decision-making classification tree was worked out.

CONCLUSION:

The produced model is sufficient for predicting IVF treatment failure and allows producing reasonable treatment tactics as well as encourages IVF treatment effectiveness improvement in patients with endometriosis.

 

 

Pol J Vet Sci. 2016 Sep 1;19(3):609-617.

Estradiol Reduces Connexin43 Gap Junctions in the Uterus during Adenomyosis in Cows.

Korzekwa AJ, Łupicka M, Socha BM, Szczepańska AA.

 

Abstract

Adenomyosis is defined as the presence of glandular foci external to the endometrium of the uterus, either in the myometrium or/and perimetrium, depending on the progress of this dysfunction. To date, we showed that steroids secretion and prolactin expression and proliferative processes are disturbed during uterine adenomyosis in cows. During endometriosis in eutopic endometrium in women, gap junctions are down regulated. The transmembrane gap junction protein, connexin (Cx43) is necessary for endometrial morphological, biochemical and angiogenic functions. The aim of this study is recognition of adenomyosis etiology by determination of the role of Cx43 in this process. Immunolocalization and comparison of Cx43 mRNA and protein expression in healthy (N=9) and adenomyotic uterine tissue (N=9), and Cx43 mRNA expression (real time PCR) in uterine stromal – myometrium co-culture under 24-hour stimulation with 17-beta estradiol (10-7M) isolated from healthy (N=5) and adenomyotic (N=5) cows were determined. Cx43 was localized in healthy and adenomyotic uteri. mRNA and protein expression was down-regulated in uterine tissue in adenomyotic compared with healthy cows (p<0.05). Estradiol stimulated Cx43 mRNA expression in myometrial cell culture and co-culture of stromal and myometrial cells in adenomyotic compared with healthy cows (p<0.05). In summary, down-regulation of Cx43 expression in the junction zone might play an important role in pathogenesis of adenomyosis. Estradiol modulates gap junctions during adenomyosis.

 

 

Reprod Biol Endocrinol. 2016 Oct 19;14(1):69.

Abdominal ectopic pregnancy after in vitro fertilization and single embryo transfer: a case report and systematic review.

Yoder N¹, Tal R², Martin JR¹.

 

Abstract

BACKGROUND:

Ectopic pregnancy is the leading cause of maternal morbidity and mortality during the first trimester and the incidence increases dramatically with assisted-reproductive technology (ART), occurring in approximately 1.5-2.1 % of patients undergoing in-vitro fertilization (IVF). Abdominal ectopic pregnancy is a rare yet clinically significant form of ectopic pregnancy due to potentially high maternal morbidity. While risk factors for ectopic pregnancy after IVF have been studied, very little is known about risk factors specific for abdominal ectopic pregnancy. We present a case of a 30 year-old woman who had an abdominal ectopic pregnancy following IVF and elective single embryo transfer, which was diagnosed and managed by laparoscopy. We performed a systematic literature search to identify case reports of abdominal or heterotopic abdominal ectopic pregnancies after IVF. A total of 28 cases were identified.

RESULTS:

Patients’ ages ranged from 23 to 38 (Mean 33.2, S.D. = 3.2). Infertility causes included tubal factor (46 %), endometriosis (14 %), male factor (14 %), pelvic adhesive disease (7 %), structural/DES exposure (7 %), and unexplained infertility (14 %). A history of ectopic pregnancy was identified in 39 % of cases. A history of tubal surgery was identified in 50 % of cases, 32 % cases having had bilateral salpingectomy. Transfer of two embryos or more (79 %) and fresh embryo transfer (71 %) were reported in the majority of cases. Heterotopic abdominal pregnancy occurred in 46 % of cases while 54 % were abdominal ectopic pregnancies.

CONCLUSIONS:

Our systematic review has revealed several trends in reported cases of abdominal ectopic pregnancy after IVF including tubal factor infertility, history of tubal ectopic and tubal surgery, higher number of embryos transferred, and fresh embryo transfers. These are consistent with known risk factors for ectopic pregnancy following IVF. Further research focusing on more homogenous population may help in better characterizing this rare IVF complication and its risks.

 

 

J Obstet Gynaecol Res. 2017 Jan;43(1):157-163.

Enlarged uterine corpus vol ume in women with endometriosis: Assessment using three-dimensional reconstruction of pelvic magnetic resonance images.

Koshiba A¹, Mori T¹, Ito F¹, Tanaka Y¹, Takaoka O¹, Takahata A², Kitawaki J¹.

 

Abstract

AIM:

To assess and compare the uterine volume and endometrium length between women with and without endometriosis, using pelvic magnetic resonance imaging scans.

METHODS:

In this case-control study, a total of 75 nulligravid women (aged 20-45 years) with regular menstrual cycles whose uterus were free of any surgically confirmed lesions were enrolled. The endometriosis group underwent surgery for endometrioma (n = 39), and the control group underwent surgery for non-endometrioma ovarian cysts (n = 36). The primary outcome was uterine corpus volume, which was assessed using three-dimensional reconstructions of preoperative pelvic magnetic resonance imaging scans.

RESULTS:

The mean uterine volume was significantly larger in the endometriosis group than in the control group (mean ± standard deviation, 50.9 ± 14.4 cm³ vs 41.7 ± 14.3 cm³ ; P < 0.01). The longitudinal length and transverse diameter of the corpus and the longitudinal length of the endometrium were also significantly greater in the endometriosis group (all, P < 0.01).

CONCLUSIONS:

An increase in uterine volume and endometrium length was observed in women with endometriosis.

 

 

 

Am J Reprod Immunol. 2016 Dec;76(6):491-498.

Alpha-7 nicotinic acetylcholine receptor (nAChR) agonist inhibits the development of endometriosis by regulating inflammation.

Yamada-Nomoto K¹, Yoshino O¹, Akiyama I², Ushijima A¹, Ono Y¹, Shima T¹, Nakashima A¹, Hayashi S³, Kadowaki M³, Osuga Y², Saito S¹.

 

Abstract

OBJECTIVE:

We investigated α-7 nAchR expression in human peritoneal macrophages and examined whether activation of nAchR might be a new therapy for endometriosis.

MATERIALS AND METHODS:

Human peritoneal fluid mononuclear cells (PFMC) were stimulated with lipopolysaccharide (LPS) in the presence of α-7 nAChR agonists. In a murine endometriosis model, α-7 nAChR modulators were administered.

RESULTS:

Human PFMC expressed α-7 nAChR at the mRNA and protein levels. Activation of α-7 nAChR with its agonists led to significant (P<.01) suppression of LPS-induced interleukin (IL) -1β expression. In a murine endometriosis model, one week after inoculation of endometrium to the peritoneal cavity, α-7 nAChR agonist significantly suppressed the expression of IL-1β mRNA (P<.01), which was negated when α-7 nAChR antagonist was administered simultaneously. α-7 nAChR agonist significantly suppressed the formation of endometriotic lesions, which was reversed with α-7 nAChR antagonist.

CONCLUSION:

Activation of nAChR might be a new candidate for treatment of endometriosis.

 

 

Mod Pathol. 2017 Feb;30(2):297-303.

CCNE1 copy-number gain and overexpression identify ovarian clear cell carcinoma with a poor prognosis.

Ayhan A^1,2,3,4, Kuhn E⁵, Wu RC⁶, Ogawa H², Bahadirli-Talbott A¹, Mao TL⁷, Sugimura H³, Shih IM^1,8, Wang TL^1,8.

 

Abstract

Ovarian clear cell carcinoma is a unique type of ovarian cancer, often derived from endometriosis, and advanced-stage disease has a dismal prognosis primarily due to the resistance to conventional chemotherapy. Previous studies have shown frequent somatic mutations in ARID1A, PIK3CA, hTERT promoter, and amplification of ZNF217; however, the molecular alterations that are associated with its aggressiveness remain largely unknown. This study examined and compared cyclin E1 expression in endometriosis-related ovarian tumors, with the aim of determining the relationship between hTERT mutations and ARID1A expression and evaluating the effects of these molecular alterations on patient survival. We performed immunohistochemistry on 207 tumors [clear cell carcinoma (n=120), endometrioid carcinoma (n=49), and seromucinous tumors (n=38)], followed by two-color fluorescence in situ hybridization (n=88) and compared with ARID1A expression and hTERT promoter mutations in the same samples. Cyclin E1 overexpression and CCNE1 copy-number gain occurred in 23.3% and 14.8% of ovarian clear cell carcinomas, respectively, but they were not detected in any of the other endometriosis-related tumors. All cases with CCNE1 copy-number gain demonstrated an intense cyclin E1 immunoreactivity (P<0.001). Cyclin E1 overexpression was positively correlated with hTERT promoter mutations (P=0.01), but not with the loss of ARID1A expression. A multivariate analysis revealed that CCNE1 overexpression predicts poor overall survival, even after adjusting for stage and age. Specifically, CCNE1 overexpression and copy-number gain were both correlated with a poor outcome in patients with stage I disease. Moreover, the subset with CCNE1 overexpression and ARID1A retention demonstrated the worst outcome. Our findings suggest that gene copy-number gain and upregulation of CCNE1 occur in ovarian clear cell carcinoma and are associated with a worse clinical outcome, dictating the survival of early-stage patients, and that these molecular alterations are unique to clear cell carcinoma among different types of endometriosis-related ovarian neoplasms.

 

 

 

J Gynecol Obstet Biol Reprod (Paris). 2016 Oct;45(8):936-941.

Surgical management of endometrioma: Result of French practice survey.

Delbos L¹, Legendre G², Rousseau M², Catala L², Lefebvre-Lacoeuille C², Bouet PE², Descamps P².

 

Abstract

OBJECTIVES:

There are many national and international recommendations and guidelines for the management of patients with endometrioma. In this study, we aimed to evaluate the impact of these recommendations on the practice of French surgeons, and to assess their knowledge about the management of endometriomas.

MATERIALS AND METHODS:

A self-questionnaire has been sent to the French members of the Society of Gynecologic Surgery and Pelvic (SCGP) in May 2015.

RESULTS:

One hundred and forty-four members of the society (36 %) participated in the survey. Most of the practitioners (71 %) followed recommendations of the Collège National des Gynécologues Obstétriciens (CNGOF), 38 % followed the guidelines of European Society of Human Reproduction and Embryology (ESHRE). One hundred percent of the surgeons declared that they practice laparoscopy when a surgical removal of the endometrioma is indicated. About treatment with GnRH analogue, 38 % of the practitioners declared that they prescribe an add back therapy immediately after the surgery, 43 % at 3 months, and 14 % declared that they never prescribe this treatment.

CONCLUSIONS:

French surgeons consider the recommendations are useful in their clinical practice; they primarily apply the guidelines of the CNGOF.

 

 

J Gynecol Obstet Biol Reprod (Paris). 2016 Oct;45(8):985-989.

About a case of uterine per-partum rupture, 37months after resection of a rectovaginal endometriosis nodule.

Delépine O¹, Curinier S², Agar N², Piquier-Perret G², Gallot D², Houlle C², Canis M², Pouly JL².

 

Abstract

Endometriosis is a common condition in women, whose main repercussions are painful symptoms. In addition, it was shown that endometriosis was a major cause of infertility and various obstetric complications could be related to this pathology. Uterine rupture is a rare but serious complication whose incidence tends to decrease with the screening of women at risk, however, its fetal, maternal morbidity and mortality causes remains important. We were confronted with a case of posterior uterine rupture in a patient of 36 years, primipare term exceeded in immediate postpartum period. The patient’s primary antecedent of uterine surgery torus was responsible for infertility endometriosis. The outcome was favorable for the mother, after a surgical treatment by laparotomy, and for the child. In the literature, two cases have been reported of uterine rupture after endometriosis surgery, which is why we found it interesting to report this rare case. Given the increase in surgical management of this disease, it seems relevant to ask whether, in the future, we should be more vigilant in monitoring pregnancy for these women.

 

 

Gynecol Obstet Fertil. 2016 Oct;44(10):541-547.

In vitro fertilization outcomes after ablation of endometriomas using plasma energy: A retrospective case-control study.

Motte I¹, Roman H², Clavier B¹, Jumeau F³, Chanavaz-Lacheray I¹, Letailleur M¹, Darwish B¹, Rives N⁴.

 

Abstract

OBJECTIVE:

Ovarian endometrioma ablation using plasma energy appears to be a valuable alternative to cystectomy, because it could spare underlying ovarian parenchyma resulting in high spontaneous and overall pregnancy rates. After initial postoperative decrease, anti-mullerian hormone (AMH) level progressively increases several months after ablation. The aim of our study was to assess the outcomes of in vitro fertilization (IVF) in women managed for ovarian endometriomas by ablation using plasma energy, when compared to those in women free of endometriosis.

METHODS:

Retrospective preliminary case-control study, enrolling women undergoing IVF or IntraCytoplasmic Sperm Injection (ICSI), from July 2009 to December 2014. Cases were infertile women with previous ovarian endometrioma ablation using plasma energy and were matched by age, AMH level and assisted reproductive technique with controls presumed free of endometriosis. IVF/ICSI response (type of protocol, dose of gonadotrophin, number of oocytes, fertilization rate) and outcomes were compared between the two groups.

RESULTS:

In all, 37 cases were compared to 74 controls. Age (30.9±4.4 years vs. 31.7±4.2 years), AMH level (2.8±2ng/mL vs. 2.8±1.7ng/mL) and ART procedures (ICSI in 24.3% vs. 27%) were comparable between the two groups. Of the 37 cases, previous surgical procedures on right and left ovaries were performed in 27% and 21.6% of patients respectively, 81% of patients were nullipara. AFSr score was 73±41, while deep endometriosis infiltrated the rectum and the sigmoid colon in respectively 40.5% and 27% of patients. Despite a lower number of oocytes retrieved, cases presented better implantation rate, pregnancy and delivery rates per cycle, oocyte retrieval, transfer, and embryo, as well as superior cumulative birth rate per transfer.

CONCLUSION:

Ovarian endometrioma ablation using plasma energy is followed by good IVF/ICSI outcomes, suggesting that surgical procedure spares underlying ovarian parenchyma. These results consolidate those of previous studies reporting high spontaneous conception rate. Hence, ovarian endometrioma ablation using plasma energy appears to be a valuable alternative to cystectomy in patients presenting with endometriosis and pregnancy intention.

 

 

Obstet Gynecol Surv. 2016 Oct;71(10):613-619

Incarceration of the Gravid Uterus.

Shnaekel KL¹, Wendel MP¹, Rabie NZ², Magann EF³.

 

Abstract

OBJECTIVE:

The aim of this review was to describe the risk factors, clinical and radiographic criteria, and management of this rare complication of pregnancy.

METHODS:

A PubMed, Web of Science, and CINAHL search was undertaken with no limitations on the number of years searched.

RESULTS:

There were 60 articles identified, with 53 articles being the basis of this review. Multiple risk factors have been suggested in the literature including retroverted uterus in the first trimester, deep sacral concavity with an overlying sacral promontory, endometriosis, previous abdominal or pelvic surgery, pelvic or uterine adhesions, ovarian cysts, leiomyomas, multifetal gestation, uterine anomalies, uterine prolapse, and uterine incarceration in a prior pregnancy. The diagnosis is difficult to make owing to the nonspecific presenting symptoms. The diagnosis is clinical and confirmed by imaging. Magnetic resonance imaging is superior to ultrasound to accurately diagnose and elucidate the distorted maternal anatomy. Treatment is dictated by gestational age at diagnosis based on risks and benefits. The recommended route of delivery is cesarean delivery when uterine polarity cannot be corrected.

CONCLUSIONS:

Incarceration of the gravid uterus is a rare but serious complication of pregnancy. The diagnosis is clinical and confirmed with imaging, with magnetic resonance imaging being superior to delineate the distorted maternal anatomy. Reduction of the incarcerated uterus should be attempted to restore polarity and avoid unnecessary cesarean delivery.

 

 

Arch Gynecol Obstet. 2017 Jan;295(1):141-151.

New adverse obstetrics outcomes associated with endometriosis: a retrospective cohort study.

Mannini L¹, Sorbi F², Noci I², Ghizzoni V², Perelli F², Di Tommaso M³, Mattei A⁴, Fambrini M².

 

Abstract

PURPOSE:

The main aim of this study was to evaluate the incidence of endometriosis and intrahepatic cholestasis (ICP) and induction of labor in pregnant women with endometriosis compared with women without endometriosis. The secondary aim was to confirm increased incidence of already known endometriosis-related pregnancy complications in these patients.

METHODS:

This is a retrospective cohort study performed at a tertiary hospital between January 2009 and December 2014 to compare obstetrics outcome between women with endometriosis and women without endometriosis. Pregnant patients with endometriosis were included in the study group. Patients were divided in the following subgroups: patients with deep infiltrating endometriosis (DIE subgroup) and patients without deep infiltrating endometriosis (non-DIE subgroup); patients with singleton pregnancy and spontaneous conception (subgroup A) and patients with multiple pregnancy and/or patients who underwent assisted reproductive technology (subgroup B). To form a control group, for each patient with endometriosis, two patients without endometriosis were selected as the control group by means of matched sample.

RESULTS:

The study population included 262 pregnant women with endometriosis and 524 controls. Patients of the study population had significantly increased risks of placenta praevia (p < 0.05), ICP (p < 0.01), induction of labor (p < 0.01) and preterm birth (p < 0.01). DIE patients had a significantly higher percentage only of preterm birth (p < 0.01), while in non-DIE group all complications had a higher incidence except for placenta praevia, which did not differ with control. Subgroup A had a statistically higher incidence of placenta praevia (p < 0.01), ICP (p < 0.01), induction of labor (p < 0.01) and preterm birth (p < 0.01) compared to its control subgroup. There was no difference in distribution of pregnancy complications between subgroup B and control subgroup.

CONCLUSIONS:

Our results showed for the first time that women with endometriosis are at higher risk of developing ICP and experiencing an induced labor. Further studies are warranted to clarify whether the history of endometriosis might be taken into account in the antenatal care of these patients.

 

 

J Minim Invasive Gynecol. 2016 Nov – Dec;23(7):1026-1027.

Robotic Cerclage in Advanced-stage Endometriosis.

Moawad GN¹, Abi Khalil ED², Samuel D³.

 

Abstract

STUDY OBJECTIVE:

To show a stepwise surgical technique of robotic-assisted transabdominal cerclage placement in a patient with deeply infiltrative endometriosis.

DESIGN:

A step-by-step surgical tutorial using narrated video.

SETTING:

The George Washington University Hospital. Local institutional review board approval is not required for case reports (Canadian Task Force Classification III).

PATIENTS:

A 38-year-old woman with cervical incompetence and a history of infertility with 5 pregnancies accomplished by in vitro fertilization. Pregnancies were as follows: 3 first trimester losses, 1 second trimester loss, and another second trimester loss despite McDonald cerclage placement.

INTERVENTIONS:

Indications for transabdominal cerclage placement include a congenital short or amputated cervix, cervical scarring that would prevent a transvaginal approach, and failed prior vaginal cerclage [1]. Robotic-assisted abdominal cerclage placement was performed in a case of advanced rectovaginal endometriosis. Normal anatomy was restored; however, no excision of endometriosis was performed because the patient was asymptomatic and already undergoing in vitro fertilization for infertility. The procedure used a 12-mm camera port through the umbilicus, 2 ancillary 8-mm robotic ports, and a 5-mm assistant port; ¼-inch-width Mersilene tape (Ethicon, Somerville, NJ) was preloaded in the abdomen through the 12-mm port before docking. Survey of the pelvis revealed the presence of advanced rectovaginal endometriosis hindering visualization of the cervicouterine isthmi on the posterior side of the uterus. The preloaded needle was parked on the right parietal peritoneum. Before cerclage placement, retroperitoneal spaces dissection bilaterally was necessary to lateralize the ureters and mobilize the rectum away from the cervicovaginal junction where the cerclage would be placed. Anteriorly, the vesicouterine peritoneum was dissected transversely, and the bladder was dissected off the lower uterine segment. A window was created in the posterior leaf of the right broad ligament lateral to the cervicouterine junction and medial to the ureter. The uterine vessels were then skeletonized, and the needle was placed through the lateral cervical isthmus medial to the vascular bundle going posterior to anterior. The procedure was repeated on the contralateral side with the needle going in the anteroposterior direction. The tape was pulled tightly against the anterior cervical isthmus. The tape ends were tied together posteriorly. There was minimal blood loss with no complications.

CONCLUSION:

A robotic-assisted abdominal cerclage can be performed safely and effectively in patients with advanced-stage endometriosis.

 

 

 

J Minim Invasive Gynecol. 2016 Nov – Dec;23(7):1123-1129.

Segmental and Discoid Resection are Preferential to Bowel Shaving for Medium-Term Symptomatic Relief in Patients With Bowel Endometriosis.

Afors K¹, Centini G², Fernandes R³, Murtada R⁴, Zupi E⁵, Akladios C⁶, Wattiez A⁷.

 

Abstract

OBJECTIVE:

To evaluate and compare medium-term clinical outcomes and recurrence rates in the laparoscopic surgical management of bowel endometriosis comparing 3 different surgical techniques (shaving, discoid, and segmental resection).

DESIGN:

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

SETTING:

Endometriosis tertiary referral center.

PATIENTS:

A retrospective cohort of 106 patients with histological confirmation of bowel endometriosis undergoing laparoscopic surgical treatment between January 1, 2010, and September 1, 2012.

INTERVENTION:

Assessment of laparoscopic bowel shaving, discoid or segmental resection for the treatment of painful symptoms related to deep endometriosis (DE) involving the bowel with 24 months of follow-up.

MEASUREMENTS AND MAIN RESULTS:

A total of 92 patients were included in the study and were divided into 3 groups according to the surgical procedure performed (shaving, n = 47; discoid resection, n = 15; segmental resection, n = 30). All symptoms improved significantly in the immediate postoperative follow-up, with significant reduction in all visual analog scale scores for pain. Compared with the discoid resection and segmental resection groups, the shaving group had a significantly higher rate of medium-term recurrence of dysmenorrhea and dyspareunia. Furthermore, the shaving group had a higher rate of reintervention for recurrent DE lesions compared with the segmental resection group (27.6% vs 6.6%; relative risk [RR], 4.14; 95% confidence interval [CI], 1.0-17.1). Postoperative complication rates were similar across all 3 groups with a rate of major complications of 4.2% in the shaving group, 6.6% in the discoid resection group, and 6.6% in the segmental resection group. According to our data, the patients with a nodule >3 cm had an RR of 2.5 (95% CI, 1.66-3.99) of requiring bowel resection.

CONCLUSION:

All 3 treatment modalities are effective in terms of immediate symptom relief with acceptable complication rates. However, significantly higher rates of symptom recurrence and reintervention were noted in the shaving group, whereas segmental resection is more likely to be indicated in cases of large nodules.

 

 

 

J Minim Invasive Gynecol. 2016 Nov – Dec;23(7):1138-1145.

Fertility Outcomes After Ablation Using Plasma Energy Versus Cystectomy in Infertile Women With Ovarian Endometrioma: A Multicentric Comparative Study.

Mircea O¹, Puscasiu L², Resch B³, Lucas J⁴, Collinet P⁵, von Theobald P⁶, Merviel P⁷, Roman H⁸.

 

Abstract

STUDY OBJECTIVE:

To compare the probability of postoperative pregnancy in infertile women with ovarian endometrioma larger than 3 cm in diameter, managed by either ablation using plasma energy or cystectomy.

DESIGN:

A multicentric case-control study (Canadian Task Force classification II-2).

SETTING:

Six surgical departments, affiliated with 4 university hospitals and 2 private facilities.

PATIENTS:

One hundred four infertile patients with ovarian endometrioma larger than 3 cm.

INTERVENTIONS:

Endometrioma ablation using plasma energy was performed in 64 patients (61.5%) and cystectomy in 40 patients (38.5%).

MEASUREMENTS AND MAIN RESULTS:

Patients were enrolled in the CIRENDO prospective cohort database (NCT02294825) from June 2009 to June 2014 and managed in 6 different facilities. The minimum length of follow-up was 1 year. Postoperative probabilities of pregnancy in patietns and control subjects were estimated using the Kaplan-Meier method with 95% confidence intervals (CIs) and compared using the log-rank test. The Cox model was used to assess independent predictive factors for pregnancy. Patients managed by plasma energy were significantly older than patients managed by cystectomy, had significantly higher overall revised American Fertility Society (rAFS) score, and had higher rate of Douglas pouch obliteration, deep endometriosis, and colorectal localizations. After a mean follow-up of 35.3 ± 17.5 months (range, 12-60), fertility outcomes were comparable between the groups. The probability of pregnancy at 24 and 36 months after surgery in plasma energy and cystectomy groups was, respectively, 61.3% (95% CI, 48.2%-74.4%) versus 69.3% (95% CI, 54.5%-83%) and 84.4% (95% CI, 72%-93.4%) versus 78.3% (95% CI, 63.8%-90%). The Cox’s model revealed that the type of surgical procedure on ovarian endometrioma had no statistically significant impact on the probability of pregnancy, after adjustment for women’s age, bilateral cysts larger than 3 cm, colorectal endometriosis, and rAFS stage of endometriosis.

CONCLUSION:

Postoperative pregnancy rates were comparable after management of ovarian endometrioma by either ablation using plasma energy or cystectomy despite an overall higher rate of unfavorable fertility predictive factors in women managed by ablation.

 

 

 

J Minim Invasive Gynecol. 2016 Nov – Dec;23(7):1130-1137.

History of Uterine Surgery Is Not Associated With an Increased Severity of Bladder Deep Endometriosis.

Marcellin L¹, Morin C², Santulli P¹, Marzouk P¹, Bourret A³, Dousset B⁴, Borghese B², Chapron C⁵.

 

Abstract

STUDY OBJECTIVE:

To analyze whether a history of uterine surgery correlates with disease severity in patients with bladder deep infiltrating endometriosis (DIE).

DESIGN:

This was an observational, cross-sectional study using data collected prospectively (Canadian Task Force classification II-2).

SETTING:

A single university tertiary referral center.

PATIENTS:

We included all nonpregnant women younger than age 42 years who had undergone complete surgical exeresis of endometriotic lesions. For each patient, a standardized questionnaire was completed during a face-to-face interview that was conducted by the surgeon in the month preceding the surgery.

INTERVENTIONS:

One hundred seven women with histologically proven bladder DIE were enrolled in this study. For the purpose of the study, the women were assigned to 2 groups before surgery: a study group that included women with a history of a scarred uterus (SU) (SU+, n = 16) and a control group that included women without SU (SU-, n = 99). Both groups were compared in terms of their general characteristics, medical histories, surgical findings, and the severity of the disease.

MEASUREMENTS AND MAIN RESULTS:

Patient age and body mass index were higher for the SU+ group as compared to the SU- group (37.9 ± 5.6 vs 32.2 ± 4.7, p < .01, and 24.7 ± 4.9 vs 21.9 ± 2.9, p = .03, respectively). Preoperative painful symptom scores did not differ between the 2 groups. No significant difference was observed in the rates of history for surgery for endometriosis (n = 11 [68.7%] vs n = 49 [53.8], p = .27). Comparison of the anatomic distribution of the lesions did not reveal a significant difference. The total American Society for Reproductive Medicine score did not differ between the groups (32.0 ± 34.4 vs 35.5 ± 34.5, p = .71). The incidence rate of isolated bladder DIE did not differ between the 2 study groups (n = 6 [37.5%] vs n = 40 [43.9%], p = .79).

CONCLUSION:

SU before surgery for endometriosis was observed in 14.9% of cases of bladder DIE; however, this was not related to an increased severity of the disease. This observational study hence does not appear to support the pathophysiologic hypothesis of a transmyometrial source for bladder DIE.

 

 

 

PLoS One. 2016 Oct 24;11(10):e0165347

Progesterone Alleviates Endometriosis via Inhibition of Uterine Cell Proliferation, Inflammation and Angiogenesis in an Immunocompetent Mouse Model.

Li Y¹, Adur MK², Kannan A¹, Davila J¹, Zhao Y³, Nowak RA², Bagchi MK³, Bagchi IC¹, Li Q¹.

 

Abstract

Endometriosis, defined as growth of the endometrial cells outside the uterus, is an inflammatory disorder that is associated with chronic pelvic pain and infertility in women of childbearing age. Although the estrogen-dependence of endometriosis is well known, the role of progesterone in development of this disease remains poorly understood. In this study, we developed a disease model in which endometriosis was induced in the peritoneal cavities of immunocompetent female mice, and maintained with exogenous estrogen. The endometriosis-like lesions that were identified at a variety of ectopic locations exhibited abundant blood supply and extensive adhesions. Histological examination revealed that these lesions had a well-organized endometrial architecture and fibrotic response, resembling those recovered from clinical patients. In addition, an extensive proliferation, inflammatory response, and loss of estrogen receptor alpha (ERα) and progesterone receptor (PR) expression were also observed in these lesions. Interestingly, administration of progesterone before, but not after, lesion induction suppressed lesion expansion and maintained ERα and PR expressions. These progesterone-pretreated lesions exhibited attenuation in KI67, CD31, and pro-inflammatory cytokine expression as well as macrophage infiltration, indicating that progesterone ameliorates endometriosis progression by inhibiting cell proliferation, inflammation and neovascularization. Our studies further showed that suppression of global DNA methylation by application of DNA methyltransferase inhibitor to female mice bearing ectopic lesions restrained lesion expansion and restored ERα and PR expression in eutopic endometrium and ectopic lesions. These results indicate that epigenetic regulation of target gene expression via DNA methylation contributes, at least in part, to progesterone resistance in endometriosis.

 

 

Obstet Gynecol. 2016 Nov;128(5):1134-1142.

Psychotherapy With Somatosensory Stimulation for Endometriosis-Associated Pain: A Randomized Controlled Trial.

Meissner K¹, Schweizer-Arau A, Limmer A, Preibisch C, Popovici RM, Lange I, de Oriol B, Beissner F.

 

Abstract

OBJECTIVE:

To evaluate whether psychotherapy with somatosensory stimulation is effective for the treatment of pain and quality of life in patients with endometriosis-related pain.

METHODS:

Patients with a history of endometriosis and chronic pelvic pain were randomized to either psychotherapy with somatosensory stimulation (ie, different techniques of acupuncture point stimulation) or wait-list control for 3 months, after which all patients were treated. The primary outcome was brain connectivity assessed by functional magnetic resonance imaging. Prespecified secondary outcomes included pain on 11-point numeric rating scales (maximal and average global pain, pelvic pain, dyschezia, and dyspareunia) and physical and mental quality of life. A sample size of 30 per group was planned to compare outcomes in the treatment group and the wait-list control group.

RESULTS:

From March 2010 through March 2012, 67 women (mean age 35.6 years) were randomly allocated to intervention (n=35) or wait-list control (n=32). In comparison with wait-list controls, treated patients showed improvements after 3 months in maximal global pain (mean group difference -2.1, 95% confidence interval [CI] -3.4 to -0.8; P=.002), average global pain (-2.5, 95% CI -3.5 to -1.4; P<.001), pelvic pain (-1.4, 95% CI -2.7 to -0.1; P=.036), dyschezia (-3.5, 95% CI -5.8 to -1.3; P=.003), physical quality of life (3.8, 95% CI 0.5-7.1, P=.026), and mental quality of life (5.9, 95% CI 0.6-11.3; P=.031); dyspareunia improved nonsignificantly (-1.8, 95% CI -4.4 to 0.7; P=.150). Improvements in the intervention group remained stable at 6 and 24 months, and control patients showed comparable symptom relief after delayed intervention.

CONCLUSION:

Psychotherapy with somatosensory stimulation reduced global pain, pelvic pain, and dyschezia and improved quality of life in patients with endometriosis. After 6 and 24 months, when all patients were treated, both groups showed stable improvements.

 

 

Obstet Gynecol. 2016 Nov;128(5):1025-1031.

Laparoscopically Confirmed Endometriosis and Breast Cancer in the Nurses’ Health Study II.

Farland LV¹, Tamimi RM, Eliassen AH, Spiegelman D, Hankinson SE, Chen WY, Missmer SA.

 

Abstract

OBJECTIVE:

To investigate the association between laparoscopically confirmed endometriosis and the risk of breast cancer. Previous research on endometriosis and breast cancer has reported mixed results.

METHODS:

Our prospective cohort study included 116,430 women from the Nurses’ Health Study II cohort followed from 1989 until 2013. Our primary analysis investigated the association between self-reported laparoscopically confirmed endometriosis and the risk of breast cancer. Breast cancer diagnosis was verified through medical records. Multivariable adjusted Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Breast cancer was further classified by menopausal status at the time of diagnosis and tumor hormone receptor status verified through tissue microarrays when available and medical records.

RESULTS:

At baseline, 5,389 (5%) women reported laparoscopically confirmed endometriosis. Over 24 years of follow-up, 4,979 (3%) incident breast cancer cases were diagnosed. Women with endometriosis were not at higher risk for overall (adjusted HR 0.96, 95% CI 0.88-1.06), premenopausal (adjusted HR 1.05, 95% CI 0.89-1.23), or postmenopausal breast cancer (adjusted HR 0.93, 95% CI 0.80-1.07). However, associations varied by tumor hormone receptor status (P value, test for heterogeneity: .001), although women with endometriosis were not at increased risk of estrogen- and progesterone receptor-positive (ER+/PR+) tumors (adjusted HR 1.00, 95% CI 0.87-1.14) or ER- and PR- tumors (adjusted HR 0.90, 95% CI 0.67-1.21). Women with endometriosis reported 2.87 ER+/PR- breast cancer cases per 10,000 person-years compared with women without endometriosis (1.32/10,000 person-years), which resulted in nearly a twofold increased risk of ER+/PR- breast cancers (adjusted HR 1.90, 95% CI 1.44-2.50).

CONCLUSION:

Endometriosis was not found to be associated with overall risk of breast cancer in this study; however, endometriosis was significantly associated with an increased risk of ER+/PR- breast tumors, which should be interpreted cautiously.

 

 

 

World Neurosurg. 2017 Jan;97:760.e1-760.

Cyclic Sciatica and Back Pain Responds to Treatment of Underlying Endometriosis: Case Illustration.

Uppal J¹, Sobotka S², Jenkins AL 3rd³.

 

Abstract

BACKGROUND:

Multiple causes outside the spine can mimic spinal back pain. Endometriosis is an important gynecologic disorder, which commonly affects the lower region of the female pelvis and less frequently the spine and soft tissues. The lumbosacral trunk is vulnerable to pressure from any abdominal mass originating from the uterus and the ovaries. Therefore symptoms of endometriosis include severe reoccurring pain in the pelvic area as well as lower back and abdominal pain.

CASE DESCRIPTION:

We report on a 39-year-old gymnast with cyclic sciatica and back pain, whose initial presentation initially led to a spinal fusion at L4/5 and L5/S1, but that procedure did not change her symptoms. Her diagnosis of endometriosis was not made until 2 years after her spinal fusion. Ultimately, once diagnosed with endometriosis of the retroperitoneal spinal and neural elements, her back and leg pain responded completely to hormonal therapy and then to a hysterectomy and a bilateral salpingo-oophorectomy. Because her true diagnosis of endometriosis was unknown and she had some degenerative changes in her spine, she underwent a spinal fusion that would probably not have been done if the diagnosis of endometriosis had been suggested.

CONCLUSIONS:

It is critical for any clinician who deals with back pain to at least consider the diagnosis of endometriosis in female patients who have a history of pelvic pain. The diagnosis of endometriosis should be considered in candidate patients by asking whether there is a significant hormonal cyclic nature to the symptoms, to prevent such unnecessary surgical adventures.

 

 

Nan Fang Yi Ke Da Xue Xue Bao. 2016 Oct 20;36(10):1369-1376.

Effect of hypobaric hypoxic preconditioning on surgically induced endometriosis by allotransplant of uterine tissue in rats.

Zhao J¹, Liu X, Li YL, Tang MH.

 

Abstract

OBJECTIVE:

To determine the effects of hypobaric hypoxia pretreatment on surgically induced endometriosis in rats.

METHODS:

Six rats were randomized into 2 groups and exposed to hypoxia (8% O₂) and normoxia (21% O₂) for 8 h. The uterine endometrium was intraperitoneally implanted into estrogen-treated ovariectomized Lewis rat, and the growth and quality of the implants were measured. The changes in apoptosis, protein and gene expressions in the serum, abdominis effusion fluids and implants were tested by ELISA, immunohistochemical staining, TUNNEL assay, Western blotting and RT-PCR.

RESULTS:

The volume of the implants in the hypoxic pretreatment group was significantly increased compared with the normoxia group. High expressions of Ki67, CD31, VEGF, and HIF-1α and lowered cell apoptosis were found in the hypoxia-pretreated implants compared with the normoxic group. VEGF level in the serum and peritoneal fluid were increased in hypoxia-pretreated group, but TNFα level was comparable between the 2 groups.

CONCLUSION:

Hypoxia play an important role in the occurrence and progression of endometriosis by increasing cell proliferation and angiogenesis and decreasing cell apoptosis in the implants in the rat model.

 

 

J Clin Endocrinol Metab. 2017 Jan 1;102(1):141-149.

Progesterone Resistance in Endometriosis Is Modulated by the Altered Expression of MicroRNA-29c and FKBP4.

Joshi NR¹, Miyadahira EH², Afshar Y³, Jeong JW¹, Young SL⁴, Lessey BA⁵, Serafini PC⁶, Fazleabas AT¹.

 

Abstract

CONTEXT:

Endometriosis results in aberrant gene expression in the eutopic endometrium (EuE) and subsequent progesterone resistance. MicroRNA (miR) microarray data in a baboon model of endometriosis showed an increased expression of miR-29c.

OBJECTIVES:

To explore the role of miR-29c in progesterone resistance in a subset of women with endometriosis.

DESIGN:

MiR-29c expression was analyzed in the endometrium of baboons and women with or without endometriosis. The role in progesterone resistance and decidualization was analyzed by transfecting human uterine fibroblast cells with miR-29c.

PATIENTS:

Subjects diagnosed with deep infiltrative endometriosis (DIE) by transvaginal ultrasound with bowel preparation underwent surgical excision of endometriosis. Eutopic secretory endometrium was collected pre- and postoperatively. Women with normal EuE and without DIE served as controls.

RESULTS:

Quantitative reverse transcription polymerase chain reaction demonstrated that miR-29c expression increased, while the transcript levels of its target, FK506-binding protein 4 (FKBP4), decreased in the EuE of baboons following the induction of endometriosis. FKBP4 messenger RNA and decidual markers were statistically significantly decreased in decidualized human uterine fibroblast cells transfected with a miR-29c mimic compared with controls. Human data corroborated our baboon data and demonstrated higher expression of miR-29c in endometriosis EuE compared with normal EuE. MiR-29c was significantly decreased in endometriosis EuE postoperatively compared with preoperative tissues, and FKBP4 showed an inverse trend following radical laparoscopic resection surgery.

CONCLUSIONS:

We demonstrate that miR-29c expression is increased in EuE of baboons and women with endometriosis, which might contribute to a compromised progesterone response by diminishing the levels of FKBP4. Resection of DIE is likely to reverse the progesterone resistance associated with endometriosis in women.

 

 

Korean J Gastroenterol. 2016 Oct 25;68(4):214-217.

A Case of Cecal Endometriosis Presenting as Subepithelial Tumor.

Hwang MS¹, Kim YD¹, Shin SY¹, Jun JH¹, Hong JS¹, Eom DW², Cheon GJ¹.

 

Abstract

Endometriosis is a benign gynecologic disease, characterized by the presence and growth of functional endometrial-like tissue outside uterus. This ectopic endometrial tissue is most commonly found in the peritoneum, ovaries and uterosacral ligaments, but extremely rarely there is involvement of the appendix or cecum. Here we report a case of cecal endometriosis presenting as a subepithelial tumor diagnosed by surgical excision.

 

 

J Obstet Gynaecol Res. 2016 Nov;42(11):1534-1540.

Analysis of pregnancy outcome and decline of anti-Müllerian hormone after laparoscopic cystectomy for ovarian endometriomas.

Taniguchi F¹, Sakamoto Y², Yabuta Y², Azuma Y², Hirakawa E², Nagira K², Uegaki T², Deura I², Hata K³, Harada T².

 

Abstract

AIM:

Excision of ovarian endometrioma (OE) may induce the reduction of ovarian reserve. We evaluated pregnancy outcomes after laparoscopic cystectomy (LC), and the pre- and postoperative levels of anti-Müllerian hormone (AMH) to consider the ovarian reserve.

METHODS:

We enrolled 40 women with OE and 16 women with benign ovarian tumors who hoped to have a child and who underwent LC. To evaluate the ovarian reserve of 40 patients (OE group, n = 24; non-OE group, n = 16), we measured serum AMH levels before and after the surgery.

RESULTS:

In the 40 women who underwent LC for OE, the cumulative pregnancy rate was 50%. Prior to the cystectomy, serum AMH levels in the OE group, especially in patients over the age of 35, were significantly lower than those in the non-OE group. Rate of decline in serum AMH in the OE group was significant compared with that in the non-OE group 6 months after surgery. In patients over the age of 35 in the OE group, AMH levels 1 year after surgery decreased noticeably.

CONCLUSION:

LC for OE could be a preferred surgical approach, but effective therapeutic strategies will have to be developed to prevent damage to the ovarian reserve, especially for older patients.

 

 

J Clin Lab Anal. 2016 Nov;30(6):831-837.

Association of the Precursor of Interleukin-1β and Peritoneal Inflammation-Role in Pathogenesis of Endometriosis.

Sikora J¹, Mielczarek-Palacz A², Kondera-Anasz Z².

 

Abstract

BACKGROUND:

The most important proinflammatory cytokine is interleukin (IL)-1β, however its precursor, prointerleukin-1β (proIL-1β), can also potentiate inflammatory state. The aim of this study was to explore the involvement of proIL-1β in pathogenesis of endometriosis. For this purpose, we evaluated concentrations of proIL-1β, IL-1β, and soluble IL-1 receptor type 2 (sIL-1R2) in peritoneal fluid (PF) and macrophage culture medium of women with endometriosis.

METHODS:

PF from 55 women with and without endometriosis was collected during laparoscopy. Peritoneal macrophages were cultured in basal and stimulated with lipopolysaccharide (LPS) conditions. Concentrations of cytokines were measured with enzyme-linked immunosorbent assays (ELISA).

RESULTS:

PF proIL-1β and IL-1β levels in endometriosis women were higher than in the control. Higher basal and stimulated macrophage secretion of cytokines in endometriosis patients than in the control was observed. However, in endometriosis, there was a higher level of proIL-1β than for the mature molecule. Additionally, lower PF and macrophages culture medium sIL-1R2 levels were observed in women with endometriosis.

CONCLUSIONS:

Abnormal proIL-1β concentration in PF and higher macrophage secretion can escalate peritoneal inflammation and endometriosis formation. The results are presented as a total IL-1β, which is a sum of proIL-1β  and IL-1β, and we believe that it reflects the actual cytokine production. The imbalance among all studied cytokines in endometriosis may be linked with an ability to transform acute inflammation to the chronic inflammation.

 

 

Am J Obstet Gynecol. 2016 Nov;215(5):589.e1-589.e6.

Effect of surgery on ovarian reserve in women with endometriomas, endometriosis and controls.

Goodman LR¹, Goldberg JM², Flyckt RL², Gupta M³, Harwalker J⁴, Falcone T².

 

Abstract

BACKGROUND:

Many women who experience endometriosis and endometriomas also encounter problems with fertility.

OBJECTIVE:

The purpose of this study was to determine the impact of surgical excision of endometriosis and endometriomas compared with control subjects on ovarian reserve.

STUDY DESIGN:

This was a prospective cohort study of 116 women aged 18-43 years with pelvic pain and/or infertility who underwent surgical treatment of suspected endometriosis (n=58) or endometriomas (n=58). Based on surgical findings, the suspected endometriosis group was further separated into those with evidence of peritoneal disease (n=29) and those with no evidence of endometriosis (n=29). Ovarian reserve was measured by anti-Müllerian hormone and compared before surgery and at 1 month and 6 months after surgery.

RESULTS:

Baseline anti-Müllerian hormone values were significantly lower in the endometrioma vs negative laparoscopy group (1.8 ng/mL [95% confidence interval, 1.2-2.4 ng/mL] vs 3.2 ng/mL [95% confidence interval, 2.0-4.4 ng/mL]; P<.02), but the peritoneal endometriosis group was not significantly different than either of these groups. Only patients with endometriomas had a significant decline in ovarian reserve at 1 month (-48%; 95% confidence interval, -54 to -18%; P<.01; mean anti-Müllerian hormone baseline value, 1.77-1.12 ng/mL at 1 month). Six months after surgery, anti-Müllerian hormone values continued to be depressed from baseline but were no longer significantly different. The rate of anti-Müllerian hormone decline was correlated positively with baseline preoperative anti-Müllerian hormone values and the size of endometrioma that was removed. Those with bilateral endometriomas (n=19) had a significantly greater rate of decline (53.0% [95% confidence interval, 35.4-70.5%] vs 17.5% [95% confidence interval, 3.2-31.8%]; P=.002).

CONCLUSION:

At baseline, patients with endometriomas had significantly lower anti-Müllerian hormone values compared with women without endometriosis. Surgical excision of endometriomas appears to have temporary detrimental effects on ovarian reserve.

 

 

Front Pharmacol. 2016 Oct 14;7:382.

Co-micronized Palmitoylethanolamide/Polydatin Treatment Causes Endometriotic Lesion Regression in a Rodent Model of Surgically Induced Endometriosis.

Di Paola R¹, Fusco R¹, Gugliandolo E¹, Crupi R¹, Evangelista M², Granese R³, Cuzzocrea S⁴.

 

Abstract

Endometriosis is a chronic, painful disease characterized by the presence of endometrial glands and stroma outside the uterine cavity. Palmitoylethanolamide (PEA), an endogenous fatty acid amide, has anti-inflammatory and neuroprotective effects. PEA lacks free radical scavenging activity, unlike polydatin (PLD), a natural precursor of resveratrol. The aim of this study was to investigate the effect of orally administered co-micronized PEA/polydatin [m(PEA/PLD)] in an autologous rat model of surgically induced endometriosis. Endometriosis was induced in female Wistar albino rats by auto-transplantation of uterine squares (implants) into the intestinal mesentery and peritoneal cavity. Rats were distributed into one control group and one treatment group (10 animals each): m(PEA/PLD) 10 mg/kg/day. At 28 days after surgery the relative volume of the endometrioma was determined. Endometrial-like tissue was confirmed by histology: Masson trichrome and toluidine blue were used to detect fibrosis and mast cells, respectively. The treated group displayed a smaller cyst diameter, with improved fibrosis score and mast cell number decrease. m(PEA/PLD) administration decreased angiogenesis (vascular endothelial growth factor), nerve growth factor, intercellular adhesion molecule, matrix metalloproteinase 9 expression, and lymphocyte accumulation. m(PEA/PLD) treatment also reduced peroxynitrite formation, (poly-ADP)ribose polymerase activation, IkBα phosphorylation and nuclear facor-kB traslocation in the nucleus. Our results suggested that m(PEA/PLD) may be of use to inhibit development of endometriotic lesions in rats.

 

 

J Clin Diagn Res. 2016 Sep;10(9):LD01-LD02.

Unique Application of Cryocone to Diagnose Umbilical Pilonidal Cyst.

Mallin K¹, Pemminati S².

 

Abstract

Patients with umbilical disorders who present with complaints of a mass, pain, tenderness or discharge will typically have a differential diagnosis including umbilical hernias, pyogenic granuloma, endometriosis, Sister Mary Joseph nodule and urachal or epidermoid cysts. We would add the inclusion of pilonidal sinus disease and present the case of a patient with an umbilical pilonidal cyst. The use of a cryocone with lubricating jelly, in this case, proved to be an easy and convenient method that aided in visualization and diagnosis of this fairly uncommon condition.

 

 

Reprod Biol Endocrinol. 2016 Oct 28;14(1):72.

Involvement of mesosalpinx in endometrioma is a possible risk factor for decrease of ovarian reserve after cystectomy: a retrospective cohort study.

Saito A¹, Iwase A^2,3, Nakamura T¹, Osuka S^1,4, Bayasula¹, Murase T¹, Kato N¹, Ishida C¹, Takikawa S¹, Goto M¹, Kikkawa F¹.

 

Abstract

BACKGROUND:

Serum anti-Müllerian hormone (AMH) concentration has been used to assess ovarian reserve in patients with endometriosis, especially when endometrioma surgery is involved. Previously, we reported that decreased serum AMH levels after cystectomy for endometriomas can recover to preoperative levels in some cases. In this present study, we assessed the sequential changes in serum AMH levels before and after cystectomy in terms of the state of the mesosalpinx prior to surgery.

METHODS:

The retrospective cohort study recruited 53 patients from a series of prospective studies conducted from 2009 to 2015. All patients underwent laparoscopic cystectomy for endometriomas. If either mesosalpinx was involved in the endometrioma or adnexal adhesion before cystectomy, the case was defined as ‘involved mesosalpinx’ (n = 14). If both mesosalpinx remained anatomically correct, the case was classified as ‘intact mesosalpinx’ (n = 39). Blood samples were obtained from the patients 2 weeks before surgery, and at 1 month and 1 year after surgery to assess serum AMH levels.

RESULTS:

The serum AMH levels (the involved group vs. the intact group) were 1.92 vs. 0.98 (P = 0.552) preoperatively, 0.59 vs. 1.99 (P = 0.049) at 1 month postoperatively, and 0.48 vs. 2.37 ng/mL (P = 0.007) at 1 year postoperatively. The involved mesosalpinx group showed a further decrease in serum AMH levels at 1 year postoperatively, while serum AMH levels in the intact mesosalpinx group tended to recover.

CONCLUSION:

These results suggest that pre-existing mesosalpinx disturbance, in combination with adhesiolysis, may be involved in the medium- and long-term decrease in ovarian reserve after endometrioma surgery. A disturbance in ovarian blood supply via the mesosalpinx may underlie this.

 

 

Fertil Steril. 2017 Jan;107(1):174-178.e2.

Validity of self-reported endometriosis and endometriosis-related questions in a Swedish female twin cohort.

Saha R¹, Marions L², Tornvall P².

 

Abstract

OBJECTIVE:

To examine the validity of self-reported endometriosis and to improve the reliability of questionnaires by including endometriosis-related questions.

DESIGN:

Analysis of survey questionnaire data.

SETTING:

Cross-sectional study.

PATIENT(S):

Cohort of 26, 898 female twins aged 20-60 years at interview, who participated in either of two surveys (1998-2002 or 2005-2006).

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Endometriosis diagnosis in the Swedish National Inpatient Registry (IPR).

RESULT(S):

The self-reported endometriosis diagnoses and endometriosis-related questions from a nationwide population-based twin registry were linked with the IPR. Fairly good agreement was found between the self-reported and IPR data on endometriosis. The receiver operating characteristics (ROC) curves showed fairly good predictive ability of self-reported endometriosis to have a confirmed endometriosis diagnosis in the IPR with an area under the curve (AUC) 0.79 (95% confidence interval [CI], 0.77-0.81). Further, the predictive ability increased to AUC 0.89 (95% CI, 0.88-0.90) when there was additional information about infertility and age.

CONCLUSION(S):

Our results indicate that self-reported data on endometriosis are moderately accurate and may be useful in studies when register data are not available.

 

 

Fertil Steril. 2016 Dec;106(7):1733-1741.

Pathophysiologic processes have an impact on the plasma metabolomic signature of endometriosis patients.

Vicente-Muñoz S¹, Morcillo I², Puchades-Carrasco L³, Payá V², Pellicer A⁴, Pineda-Lucena A⁵.

 

Abstract

OBJECTIVE:

To evaluate potential variations in the plasma metabolomic profile of endometriosis patients as a consequence of pathophysiologic alterations associated with this disorder.

DESIGN:

Prospective study. For each subject, a plasma sample was collected after overnight fasting and before surgery.

SETTING:

University medical center.

PATIENT(S):

The clinical cohort included 50 endometriosis patients, diagnosed at early (n = 6) and advanced (n = 44) stages of the disease, and 23 healthy women. All volunteers underwent diagnostic laparoscopy to visually confirm the presence or absence of endometriotic lesions.

INTERVENTION(S):

Metabolomic profiling of plasma samples based on ¹H-nuclear magnetic resonance (NMR) spectroscopy in combination with statistical approaches.

MAIN OUTCOME MEASURE(S):

Comparative identification of metabolites present in plasma from endometriosispatients and healthy women.

RESULT(S):

The plasma metabolomic profile of endometriosis patients was characterized by increased concentration of valine, fucose, choline-containing metabolites, lysine/arginine, and lipoproteins and decreased concentration of creatinine compared with healthy women. Metabolic alterations identified in the plasma metabolomic profile of endometriosis patients correlate with pathophysiologic events previously described in the progression of this disease.

CONCLUSION(S):

The results highlight the potential of ¹H-NMR-based metabolomics to characterize metabolic alterations associated with endometriosis in plasma samples. This information could be useful to get a better understanding of the molecular mechanisms involved in the pathogenesis of endometriosis, thus facilitating the noninvasive diagnosis of this pathology at early stages.

 

 

Fertil Steril. 2017 Jan;107(1):167-173.

Mannose receptor is highly expressed by peritoneal dendritic cells in endometriosis.

Izumi G¹, Koga K², Takamura M¹, Makabe T¹, Nagai M¹, Urata Y¹, Harada M¹, Hirata T¹, Hirota Y¹, Fujii T¹, Osuga Y¹.

 

Abstract

OBJECTIVES:

To characterize peritoneal dendritic cells (DCs) in endometriosis and to clarify their role in its etiology.

DESIGN:

Experimental.

SETTING:

University hospital.

PATIENT(S):

Sixty-three women (35 patients with endometriosis and 28 control women) who had undergone laparoscopic surgery.

INTERVENTION(S):

Peritoneal DCs from endometriosis and control samples were analyzed for the expression of cell surface markers. Monocyte-derived dendritic cells (Mo-DCs) were cultured with dead endometrial stromal cells (dESCs) to investigate changes in phagocytic activity and cytokine expression.

MAIN OUTCOME MEASURE(S):

Cell surface markers and cytokine expression and identification with the use of flow cytometry or reverse-transcription polymerase chain reaction (RT-PCR). Changes in cytokine expression and phagocytic activity of Mo-DCs cultured with dESCs and d-mannan were measured with the use of flow cytometry and RT-PCR.

RESULT(S):

The proportion of mannose receptor (MR)-positive myeloid DC type 1 was higher in endometriosis samples than in control samples. The blocking of MR reduced phagocytosis of dESCs by Mo-DCs. Mo-DCs cultured with dESCs expressed higher levels of interleukin (IL) 1β and IL-6 than control samples.

CONCLUSION(S):

Peritoneal DCs in endometriosis tissue express high levels of MR, which promotes phagocytosis of dead endometrial cells and thereby contributes to the etiology of endometriosis.