Trending in Altmetric
This article is in the top 10% of similar research outputs scored by Altmetric,
a service which tracks the online attention articles have received.
McMaster PLUS Selected
This article has been identified as especially clinically relevant or newsworthy by at least 3
practicing clinicians and of high scientific quality by expert researchers
as a part of the McMaster PLUS article rating service.
BACKGROUND: The longer term cardiovascular effects of fertility therapy are unknown.
OBJECTIVES: The aim of this study was to summarize data linking fertility therapy with subsequent cardiovascular outcomes.
METHODS: We systematically searched published reports for studies addressing the question "does fertility therapy increase the risk of longer term cardiovascular outcomes?" We included: 1) human studies; 2) case control, cohort, or randomized designs with 3) exposure to fertility therapy and 4) cardiovascular outcomes clearly reported; 5) presence of comparison group; 6) minimum 1-year follow-up; and 7) adjustment for age. Two independent reviewers screened abstracts, titles, and full texts, and assessed study quality. We used the DerSimonian and Laird random-effects models to pool hazard ratios (HRs) with 95% confidence intervals (CIs) of the following outcomes: acute cardiac event; stroke; venous thromboembolism; hypertension; and diabetes mellitus, comparing women who received fertility therapy with those who did not.
RESULTS: Six observational studies met inclusion criteria including 41,910 women who received fertility therapy and 1,400,202 women who did not. There was no increased risk of a cardiac event (pooled HR: 0.91; 95% CI: 0.67 to 1.25; I(2) = 36.6%), or diabetes mellitus (pooled HR: 0.93; 95% CI: 0.87 to 1.001; I(2) = 0%). Results were not pooled for hypertension (I(2) = 95.0%) and venous thromboembolism (I(2) = 82.3%). There was a trend toward higher risk of stroke (pooled HR: 1.25; 95% CI: 0.96 to 1.63; I(2) = 0%).
CONCLUSIONS: The small number of studies and significant heterogeneity precludes definitive reassurance about the longer term cardiovascular safety of these treatments, particularly stroke. Future studies are needed to address ongoing knowledge gaps in this area.
AbstractText: Recent breast cancer treatment guidelines recommend that higher-risk premenopausal patients should receive ovarian function suppression (OFS) as part of adjuvant endocrine therapy. If chemotherapy is also given, it is uncertain whether to select concurrent or sequential OFS initiation AbstractText: We analyzed 1872 patients enrolled in the randomized phase III TEXT and SOFT trials who received adjuvant chemotherapy for ...
Oocyte maturation arrest results in female infertility, but the genetic determinants of human oocyte maturation arrest remain largely unknown. Previously, we identified TUBB8 mutations responsible for human oocyte maturation arrest, indicating the important role of genetic factors in the disorder. However, TUBB8 mutations account for only around 30% of individuals with oocyte maturation arrest; thus, the disorder is likely to involve other genetic factors that are as yet unknown. Here, we initially identified a homozygous nonsense mutation of PATL2 (c.784C>T [p.Arg262(∗)]) in a consanguineous family with a phenotype characterized by human oocyte germinal vesicle (GV) arrest. Subsequent mutation screening of PATL2 in a cohort of 179 individuals identified four additional independent individuals with compound-heterozygous PATL2 mutations with slight phenotypic variability. A genetic burden test further confirmed the genetic contribution of PATL2 to human oocyte maturation arrest. By western blot in HeLa cells, identification of splicing events in affected individuals' granulosa cells, and immunostaining in affected individuals' oocytes, we provide evidence that mutations in PATL2 lead to decreased amounts of protein. These findings suggest an important role for PATL2 mutations in oocyte maturation arrest and expand our understanding of the genetic basis of female infertility.
OBJECTIVE: To investigate the efficacy and safety of ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen (FlexibleMIB) compared with placebo to treat endometriosis-associated pelvic pain (EAPP).
DESIGN: A phase 3, randomized, double-blind, placebo-controlled, parallel-group study, consisting of a 24-week double-blind treatment phase followed by a 28-week open-label extension phase with an unblinded reference arm.
SETTING: Thirty-two centers.
PATIENT(S): A total of 312 patients with endometriosis.
INTERVENTION(S): Patients were randomized to FlexibleMIB, placebo, or dienogest. The FlexibleMIB and placebo arms received 1 tablet per day continuously for 120 days, with a 4-day tablet-free interval either after 120 days or after ≥3 consecutive days of spotting and/or bleeding on days 25-120. After 24 weeks, placebo recipients were changed to FlexibleMIB. Patients randomized to dienogest received 2 mg/d for 52 weeks in an unblinded reference arm.
MAIN OUTCOME MEASURE(S): Absolute change in the most severe EAPP based on visual analog scale scores from the baseline observation phase to the end of the double-blind treatment phase.
RESULT(S): Compared with placebo, FlexibleMIB significantly reduced the most severe EAPP (mean difference in visual analog scale score: -26.3 mm). FlexibleMIB also improved other endometriosis-associated pain and gynecologic findings and reduced the size of endometriomas.
CONCLUSION(S): FlexibleMIB improved EAPP and was well tolerated, suggesting it may be a new alternative for managing endometriosis.
CLINICAL TRIALS REGISTRATION NUMBER: NCT01697111.
Bowel endometriosis can affect the ileum in 2-16% of women with endometriosis. Here we report a 37-year-old women with complaints of metrorrhagia, dysmenorrhea, noncyclic pelvic pain, and cyclic constipation for 10 years. Transvaginal ultrasound showed an ileum nodule compromising the muscular layer suggestive of endometriosis. At laparoscopy, it was observed two small lesions in ileum causing a severe horseshoe retraction of the small bowel submitted to surgery. Patient was submitted to enterectomy with complete resolution of symptoms.
Women's Health (5) Endometriosis (4), Metrorrhagia (1), more mentions
To analyze whether the endometrial and endometriotic microenvironment is involved in the pathogenesis of endometriosis, we characterized the stromal composition. We used CD90 for fibroblasts, α-smooth muscle actin for myofibroblasts as well as CD10 and CD140b for mesenchymal stromal cells. Quantification of eutopic endometrial stroma of cases without endometriosis showed a high percentage of stromal cells positive for CD140b (80.7%) and CD10 (67.4%), a moderate number of CD90-positive cells (57.9%), and very few α-smooth muscle actin-positive cells (8.5%). These values are highly similar to cases with endometriosis showing only minor changes: CD140b (76.7%), CD10 (63%), CD90 (53.9%), and α-smooth muscle actin (6.9%). There are no significant differences in the composition of CD140b- and CD10-positive stromal cells between the eutopic endometrial stroma and the 3 different endometriotic entities (ovarian, peritoneal, and deep infiltrating endometriosis), except for a significant difference between CD10-positive stromal cells in peritoneal lesions compared to ovarian lesions. However, the percentage of CD90-positive stromal cells was reduced in the 3 different endometriotic entities compared to the endometrium, especially significant in the ovarian lesions. In contrast, the percentage of α-smooth muscle actin-positive cells in the ovary was moderately increased. Taken together, the marker signature of eutopic endometrial and endometriotic stromal cells resembles mostly mesenchymal stromal cells. Our results show clearly that the proportion of the different stromal cell types in the endometrium with or without endometriosis does not differ significantly, thus suggesting that the stromal eutopic endometrial microenvironment does not contribute to the pathogenesis of endometriosis.
A body of evidence suggests a role for inflammation in the pathogenesis of endometriosis. Numerous case-control studies have found that inflammatory markers were elevated in endometriosis cases compared to controls. However, results are not consistent and no prior prospective study exists. We conducted a case-control study study nested within the Nurses' Health Study II examining the associations between plasma levels of interleukin-1 beta (IL-1ß), IL-6, soluble tumor necrosis factor α receptor-1 (sTNFR-1), sTNFR-2, and high-sensitivity C-reactive protein and laparoscopically-confirmed endometriosis risk. Between blood collection in 1996-1999 and 2007 we ascertained 350 incident endometriosis cases and 694 matched controls. Women in quintiles 2-4 of IL-1ß levels had an increased risk of endometriosis (2nd quintile, RR = 3.30 (95% CI = 1.06-10.3); 3rd quintile, RR = 3.36 (95% CI = 1.09-10.4); 4th quintile, RR = 4.64 (95% CI = 1.58-13.6); Ptrend = 0.62)), suggesting an association beginning at IL-1ß levels ≥0.47 pg/mL. A significant non-linear association with sTNFR-2 was observed, with an elevation in the risk of endometriosis when sTNFR-2 was > 3400 pg/ml. Plasma IL-6, sTNFR-1, and high-sensitivity C-reactive protein levels were not associated with endometriosis risk. Further research in larger studies with younger age at blood collection and longer time from blood to surgical diagnosis will be required to confirm these associations.
Women's Health (8) Endometriosis (8), Necrosis (1), Neoplasms (1), more mentions
Uterine, ovarian, and placental pathologies are among the differential considerations for a pregnant woman presenting with abdominal and pelvic pain. Imaging plays a key role in the initial work-up of these patients. Sonography is often the first line test; however, evaluation of pelvic pathology can be limited in the gravid state, especially in mid- or late-term pregnancy. We present a case of a pregnant woman who came to the emergency room at 25 weeks with acute abdominal and pelvic pain. Both ultrasound and MR imaging findings revealed intraperitoneal hemorrhage, initially of unknown origin, as well as endometriomas and deep endometriosis. Only postpartum imaging confirmed a uterine artery pseudoaneurysm (PSA) presumably due to decidual reaction in deep endometriosis. We speculate the intraperitoneal hemorrhage was subsequently due to the PSA. This case demonstrates that if hemorrhage is not recognized promptly, it can lead to hemodynamic instability, as well as premature labor and delivery.
Women's Health (3) Hemorrhage (3), Endometriosis (3), False Aneurysm (2), more mentions
Endometriotic tissues exhibit high migration ability with the underlying mechanisms remain elusive. Our previous studies have demonstrated that cystic fibrosis transmembrane conductance regulator (CFTR) acts as a tumor suppressor regulating cell migration. In the present study, we explored whether CFTR plays a role in the development of human endometriosis. We found that both mRNA and protein expression levels of CFTR and urokinase-type plasminogen activator receptor (uPAR) were significantly increased in ectopic endometrial tissues from patients with endometriosis compared to normal endometrial tissues from women without endometriosis and positively correlated. In human endometrial Ishikawa (ISK) cells, overexpression of CFTR stimulated cell migration with upregulated NFκB p65 and uPAR. Knockdown of CFTR inhibited cell migration. Furthermore, inhibition of NFκB with its inhibitors (curcumin or Bay) significantly reduced the expression of uPAR and cell migration in the CFTR-overexpressing ISK cells. Collectively, the present results suggest that the CFTR-NFκB-uPAR signaling may contribute to the progression of human endometriosis, and indicate potential targets for diagnosis and treatment.
Women's Health (5) Endometriosis (5), Cystic Fibrosis (1), Neoplasms (1), more mentions
Endometriosis is a common disease characterized by the presence of ectopic endometrial tissue. Although the pathogenesis of endometriosis remains unclear, several factors have been implicated, including the dysregulation of homeobox ( HOX) genes. Our objective was to investigate the localization and immunoreactivity of HOXB4 in endometrial tissues from women with or without endometriosis. We studied samples of eutopic endometrium (EE), endometriomas (Eoma), superficial endometriosis (SE), and deep infiltrating endometriosis (DIE) from 34 women with endometriosis, as well as eutopic endometrium from 38 women without endometriosis (EC). HOXB4 localization and immunoreactivity was assessed using immunohistochemistry and histoscore analysis. Data were analyzed with and without stratification by menstrual cycle phase. HOXB4 protein was present in the nuclei of endometrial glandular epithelial cells but not in stromal cells. HOXB4 immunoreactivity was reduced in DIE samples compared to all other groups. A smaller reduction in HOXB4 immunoreactivity was observed in SE samples compared to EC samples. HOXB4 immunoreactivity was significantly greater in proliferative compared to secretory phase samples in the EC group but not in EE, Eoma, or DIE groups. Among only proliferative phase samples, HOXB4 immunoreactivity was reduced in EE, Eoma, and DIE groups compared to EC. Based on these data, we suggest that an impaired capacity of eutopic and ectopic endometrial tissue to upregulate levels of HOXB4 during the proliferative phase may play a role in the pathogenesis of endometriosis and that further downregulation of HOXB4 may enhance ectopic implant invasiveness.
Brain-derived neurotrophic factor (BDNF) is a regulator for the formation and maintenance of chronic pain in various chronic disorders and has been shown to increase in the serum of women with endometriosis. However, BDNF expression in the peritoneal fluid (PF) and ectopic lesions and its role in endometriosis pain remain unclear. Thus, this study aims to determine the BDNF concentrations in serum and PFs and BDNF expression levels in ectopic lesions and endometriotic stromal cells (ESCs) of women with endometriosis (n = 60). The obtained results were then compared with those of women without endometriosis (n = 38). Brain-derived neurotrophic factor concentrations in serum and PF, as well as the BDNF expression levels in ectopic lesions and endometriotic cells, were evaluated through enzyme-linked immunosorbent assay, immunohistochemical staining, quantitative real-time polymerase chain reaction, and Western blot analysis. As a result, BDNF concentrations in serum and PF were significantly higher in women with endometriosis with pain (2284.3 ± 51.5 pg/mL, n = 23; 58.8 ± 6.4 pg/mL, n = 16) than in women with endometriosis without pain (1999.8 ± 61.1 pg/mL, n = 37; 31.7 ± 2.9 pg/mL, n = 25; P < .01). Moreover, BDNF messenger RNA (mRNA) expression levels in ectopic lesions (8.97 ± 1.44, n = 29) were significantly higher than eutopic (0.97 ± 0.14, n = 16; P < .01) and control endometrium (1.23 ± 0.19, n = 18; P < .01) and were correlated with endometriosis pain ( P < .05). Furthermore, increased BDNF mRNA and protein expression levels in ESCs induced by estradiol or interleukin 1β were removed using a phosphorylated extracellular-regulated protein kinase 1/2 inhibitor. These results suggest that BDNF may play an important role in the pathogenesis of endometriosis pain.
Women's Health (9) Endometriosis (9), Chronic Pain (1), more mentions
BACKGROUND: The study objective was to analyze and compare patient-reported experience measures (PREMs) and patient-reported outcome measures (PROMs) after hysterectomy in women with and without a preoperative complaint of pelvic pain associated with and without a confirmed diagnosis of endometriosis.
METHODS: Retrospective nationwide register study. Data on 28,776 hysterectomies performed on benign indication between 2004 and 2016 were retrieved from the Swedish National Register for Gynecological Surgery. Multivariable logistic regression models were used to compare the PREMs and PROMs items. The results are presented as adjusted odds ratios (aORs) and 95% confidence intervals (CI).
RESULTS: Regardless of the occurrence of pelvic pain preoperatively and a diagnosis of endometriosis, 1 year after surgery, the women were satisfied or very satisfied (>90%) with the hysterectomy, and their medical condition was improved or much improved (>95%). The women with a preoperative complaint of pelvic pain and endometriosis more often reported excessively short hospital stays (aOR 1.45, 95% CI 1.17-1.79), more severe complications after discharge (aOR 2.02, 95% CI 1.59-2.66) at the 8-week follow-up and at the 1-year follow-up (aOR 2.31, 95% CI 1.57-3.39), and more dissatisfaction with the operation (aOR 1.83, 95% CI 1.35-2.48) than preoperative pelvic pain-free women without endometriosis at the 1-year follow-up.
CONCLUSIONS: The majority of the women were satisfied after their hysterectomy. The women with pelvic pain and endometriosis were at a higher risk of being dissatisfied. Pelvic pain per se seemed to be the main factor affecting the rating in the PREMs and PROMs, and the endometriosis was a significant contributing factor.
Optimal surgical treatment of rectovaginal endometriosis remains a controversial topic. The objective of this study was to evaluate long term postoperative outcomes after rectal shaving or colorectal resection for rectovaginal endometriosis MATERIAL AND METHODS: 195 patients underwent surgery (172 managed by shaving, 23 by colorectal resection) between January 2000 and June 2013 for rectovaginal endometriosis (>2cm) involving at least the serosa of the rectum. Primary outcome measures were pain and fertility. Secondary outcome measures were complications, recurrence rates and quality of life RESULTS: Mean follow-up was 60±42 months in the shaving group and 67±47 months in the resection group. The mean VAS score for pelvic pain between the pre and postoperative period decreased from 5.5±3.5 (shaving group) and 7.3±2.9 (resection group) to 2.3±2.4 (p<0.001) and 2.0±1.8 (p<0.001) respectively. For dysmenorrhea, the mean baseline VAS score fell postoperatively from 7.7±2.8 (shaving group) and 8.2±2.6 (resection group) to 3.3±2.9 (p<0.001) and 2.7±2.7 (p<0.001) respectively. Pregnancy rates were 73% for shaving and 69% for resection. Major complications occurred in 4% of patients in the shaving group and in 26% in the resection group (p=0.001). Thirteen patients (7.6%) from the shaving group and none from the resection group were reoperated for suspicion of endometriosis recurrence (p=0.37). Postoperative quality of life scores revealed no differences between the two groups CONCLUSION: Our study demonstrates that rectal shaving, when feasible for rectovaginal nodule (>2cm) infiltrating the digestive serosa, has equal impact on pain and pregnancy rates compared to colorectal resection at long-term follow-up, with low complication and favorable pregnancy rates. This article is protected by copyright. All rights reserved.
Women's Health (6) Endometriosis (6), Infertility (1), more mentions
Study Objectives: Non-apnoea sleep disorder (NASD) increases the risk of hypertension, type 2 diabetes mellitus (DM), chronic kidney disease (CKD), cardiovascular disease and stroke. However, the risk and the time interval of NASD to female infertility has not been thoroughly understood. Our study aimed to determine whether NASD increases subsequent risk of female infertility.
Methods: This study utilized outpatient and inpatient data from the Longitudinal Health Insurance Database (LHID) between 2000 and 2010 in Taiwan. We enrolled 50,154 females aged 20 to 45 years old and diagnosed with NASD as outpatients≧2 times or hospitalized, 16,718 of them who matched our criteria were assigned to the study group. For each NASD patient, 2 comparison patients were frequency matched by age (each 5-year span), index date and comorbidities as the control cohort with a total of 33,436 patients. We conducted Cox proportional hazard regression analysis to estimate the effects of NASD on female infertility.
Results: The NASD cohort had an adjusted hazard ratio (HR) of subsequent female infertility 3.718-fold higher than that of the cohort without sleep disorders. In the stratified age group, NASD had the highest impact on 26- to 30-year-olds, with an adjusted HR of 5.146 followed by 31- to 35-year-olds (adjusted HR= 3.356). The Kaplan-Meier analysis also showed that in the sixth year of follow up, the incidence of female infertility was higher in the NASD cohort than in the general population cohort till the end of the follow up.
Conclusions: Our study demonstrates that NASD patients are at a higher risk of developing female infertility.
OBJECTIVE: To evaluate the sacral nerve root features by the means of Magnetic Resonance Imaging Diffusion Tensor Imaging (MRI-DTI) tractography in women with endometriosis and /or adenomyosis and to analyze the correlation between DTI abnormalities, pain symptoms, and endometriotic lesions found at surgery.
DESIGN: A cross-sectional, observational study (Canadian Task Force classification II-2) SETTING: University hospital PATIENTS: 76 women with clinical suspicion of endometriosis .
INTERVENTIONS: Before surgery, dysmenorrhea, deep dyspareunia and non-cyclic pelvic pain (NCPP) were assessed by the means of 10 points Visual Analog Scale (VAS). MRI was performed on 3T Magnet, and, at the end, a 3D reconstruction of S1, S2 and S3 was achieved. Fractional Anisotropy (FA) was calculated for every root. Laparoscopic treatment of endometriosis was performed in 56 cases.
MAIN OUTCOME MEASURES: Correlation between sacral root reconstruction by MRI/DTI tractography, pain symptoms and laparoscopic findings.
RESULTS: DTI of sacral roots revealed a regular and homogeneous appearance in 17 (25.8%) patients, while in 44 (66.7%) women abnormalities in microstructure reconstructions, with fiber irregularities and disorganization and loss of the simple unidirectional course, were found. At laparoscopy, ovarian endometriomas were found in 82.1% of cases and deep lesions (DIE) in 57.1%. Endometriosis was staged according to the rASRM classification. Pathological DTI was significantly associated with the severity of dysmenorrhea and NCPP, pain duration, the presence of tubo-ovarian and cul-de-sac adhesions and DIE.
CONCLUSION: The presence of pathological DTI of the sacral nerve roots correlates with the type of pain, adhesions and DIE. At present DTI can be useful for a better understanding of pain. However, DTI could become a useful tool in therapeutic planning of patients with endometriosis.
Women's Health (9) Endometriosis (7), Adenomyosis (1), Dyspareunia (1), more mentions
Adequate management of endometriosis by laparoscopy included 3 steps: a laparoscopic diagnosis with peritoneal fluid sampling for cytologic examination and biopsies of implants and of peritoneum to assure a correct diagnosis, a laparoscopic evaluation of extension with the American Fertility Society (AFS) 85 scoring system in order to classify the severity of the disease, and a laparoscopic treatment with the following strategy: drainage of the ovarian endometrioma and careful peritoneal washing, treatment of peritoneal implants, ovariolysis, treatment of the ovarian cysts, hemostasis and peritoneal lavage. Treatment of peritoneal implants is very easily performed by CO2 laser vaporization using a suprapubic puncture. Ovarian endometriomas are treated by laparoscopic cystectomy using a transparietal cystectomy or an intraperitoneal cystectomy. Laser vaporization is used only in case of small ovarian cysts or after an incomplete resection of a large cyst. Results of laparoscopic treatment of endometriosis compare favorably with those obtained with surgical procedures performed by laparotomy with the well known advantage of a laparoscopic approach.
Women's Health (4) Endometriosis (6), Ovarian Cysts (2), Cysts (1), more mentions