In women with endometriosis, including those with endometriomas, 6 to 8 weeks of continuous use of oral contraception (OC) before assisted reproduction treatment (ART) maintains ART outcomes ...comparable with the outcomes of age-matched controls without endometriosis. In contrast, ART outcomes are markedly compromised in endometriosis patients who are not pretreated with OC. Ovarian responsiveness to stimulation was not altered by 6 to 8 weeks' use of pre-ART OC, including in poor responders with endometriomas.
The time between symptoms onset and endometriosis diagnosis is usually long. The negative impacts of delayed endometriosis diagnosis can affect patients and health outcomes.
We conducted a ...case-control study using clinical symptoms and epidemiological data extracted from a prospective pre-operative patient questionnaire compared between patients with histologically proven endometriosis and patients with no endometriosis at surgical exploration from 2005 to 2018, in a French referral center. We used the beta coefficients of the significant variables introduced in a multiple regression model to devise a score (score 1), evaluated by the area under the curve (or C-index), with three levels, defined by a score between 1 and ≥ 25: (i) highly specific, identifying correctly the patients without the disease; (ii) highly sensitive, identifying the patients with the disease; and (iii) a level maximizing sensitivity and specificity for the best classification of the whole population. To minimize patient self-evaluation of pain, we devised a second score (score 2) with the same method and levels and scores definition, excluding visual analog scale pain scores, except for dysmenorrhea. These scores were validated on an internal and external population.
Score 1 had a C-index of 0.81 (95% CI 0.79–0.83). Results for the three score 1 levels were: ≥ 25: specificity of 91% (95% CI 89–93); < 11: sensitivity of 91% (95% CI 89–93); ≥ 18: specificity of 75% (95% CI 72–78) and sensitivity of 73% (95% CI 70–76). Score 2 had a C-index of 0.75 (95% CI 73–77). The three levels of score 2 were: ≥ 24: specificity of 82% (95% CI 80–85); < 7: sensitivity of 92% (95% CI 90–94); ≥ 17: specificity of 62% (95% CI 58–65) and sensitivity of 78% (95% CI 75–81). The two scores were internally and externally validated.
A score based only on a patient questionnaire could allow identification of a population at high risk of endometriosis. This strategy might help referral to specialized radiologists for a non-surgical endometriosis scan.
None.
Introduction
BAY1128688 is a selective inhibitor of aldo-keto reductase family 1 member C3 (AKR1C3), an enzyme implicated in the pathology of endometriosis and other disorders. In vivo animal studies ...suggested a potential therapeutic application of BAY1128688 in treating endometriosis. Early clinical studies in healthy volunteers supported the start of phase IIa.
Objective
This manuscript reports the results of a clinical trial (AKRENDO1) assessing the effects of BAY1128688 in adult premenopausal women with endometriosis-related pain symptoms over a 12-week treatment period.
Methods
Participants in this placebo-controlled, multicenter phase IIa clinical trial (NCT03373422) were randomized into one of five BAY1128688 treatment groups: 3 mg once daily (OD), 10 mg OD, 30 mg OD, 30 mg twice daily (BID), 60 mg BID; or a placebo group. The efficacy, safety, and tolerability of BAY1128688 were investigated.
Results
Dose-/exposure-dependent hepatotoxicity was observed following BAY1128688 treatment, characterized by elevations in serum alanine transferase (ALT) occurring at around 12 weeks of treatment and prompting premature trial termination. The reduced number of valid trial completers precludes conclusions regarding treatment efficacy. The pharmacokinetics and pharmacodynamics of BAY1128688 among participants with endometriosis were comparable with those previously found in healthy volunteers and were not predictive of the subsequent ALT elevations observed.
Conclusions
The hepatotoxicity of BAY1128688 observed in AKRENDO1 was not predicted by animal studies nor by studies in healthy volunteers. However, in vitro interactions of BAY1128688 with bile salt transporters indicated a potential risk factor for hepatotoxicity at higher doses. This highlights the importance of in vitro mechanistic and transporter interaction studies in the assessment of hepatoxicity risk and suggests further mechanistic understanding is required.
Clinical Trial Registration
NCT03373422 (date registered: November 23, 2017)
To compare potential factors associated with deep infiltrating endometriosis (DIE) versus ovarian endometrioma (OMA) among endometriosis patients in China.
A subgroup analysis of factors associated ...with DIE versus OMA was performed in Chinese women from the FEELING study. This study included 156 OMA patients and 78 DIE patients. Retrospective information on symptoms and previous medical history was collected via face-to-face interviews; patients also completed a questionnaire to provide information on current habits. Univariate and multivariate logistic regression analyses were conducted to identify potential factors that are associated with DIE versus OMA.
From univariate analysis, women who were married, at older age, had any siblings, prior pregnancy, or longer time since age at menarche on the day of visit were more likely to be diagnosed with DIE (P < 0.05). Also, the incidence of previous uterine surgery, menstrual and ovulatory disorders, deep dyspareunia, and gastrointestinal symptoms during menstruation were major factors that were significantly associated with the diagnosis of DIE (P < 0.05). Multivariate analysis showed that women with any siblings, gastrointestinal symptoms during menstruation, or eating a greater number of fruit/vegetables per day were more likely to be diagnosed with DIE. Meanwhile, eating organic food and experiencing stress were major factors that are associated with the diagnosis of OMA.
The findings provide additional information on the potential risk factors that are associated with DIE, compared with OMA among Chinese endometriosis patients. The results may help to better understand DIE versus OMA, and aid in earlier risk stratification and diagnosis of the patients.
NCT01351051 . Registered 10 May 2011.
Recently, three meta-analyses have concluded that cotreatment with GH improves assisted reproduction outcome in poor controlled ovarian stimulation responders. Although generally GH supplements did ...not increase controlled ovarian stimulation response or number of oocytes, the supplements improved pregnancy and live-birth rates—thus speaking for an effect on oocyte quality.
Objective: To investigate whether specific types of pelvic pain are correlated with the anatomic locations of deeply infiltrating endometriosis (DIE).
Design: Retrospective data analysis.
Setting: ...University tertiary referral center.
Patient(s): Two hundred and twenty-five women with pelvic pain symptoms and DIE.
Intervention(s): During surgery, we recorded the anatomic locations of DIE implants and associated endometriosis.
Main Outcome Measure(s): We studied the incidence of pelvic pain symptoms including severe dysmenorrhea, deep dyspareunia, noncyclic chronic pelvic pain, painful defecation during menstruation, urinary tract symptoms, and gastrointestinal symptoms as related to the location of DIE.
Result(s): The frequency of severe dysmenorrhea increased with Douglas pouch adhesions and decreased with parity. The frequency of dyspareunia increased with a uterosacral ligament DIE location and decreased when it involved the bladder. The frequency of noncyclic chronic pelvic pain was higher when it involved the bowel and was lower for women who were treated for infertility. The frequency of painful defecation during menstruation was higher when DIE involved the vagina; lower urinary tract symptoms were more frequent when DIE involved the bladder and less frequent in women with a lower body mass index. Gastrointestinal symptoms were associated with bowel or vaginal DIE locations.
Conclusion(s): The types of pelvic pain are related to the anatomic location of DIE. Knowledge of the characteristics of pelvic pain symptoms is important in the preoperative assessment of patients with suspected DIE.
Uterine leiomyomas (fibroids) are the most common gynaecological benign tumors in premenopausal women. Evidences support the role of oxidative stress in the development of uterine leiomyoma. We have ...analysed oxidative stress markers (thiols, advanced oxidized protein products (AOPP), protein carbonyls and nitrates/nitrites) in preoperative sera from women with histologically proven uterine leiomyoma.
We conducted a laboratory study in a tertiary-care university hospital. Fifty-nine women with histologically proven uterine leiomyoma and ninety-two leiomyoma-free control women have been enrolled in this study. Complete surgical exploration of the abdominopelvic cavity was performed in each patient. Preoperative serum samples were obtained from all study participants to assay serum thiols, AOPP, protein carbonyls and nitrates/nitrites. Concentrations of serum protein carbonyl groups and AOPP were higher in leiomyoma patients than in the control group (p=0.005 and p<0.001, respectively). By contrast, serum thiol levels were lower in leiomyoma patients (p<0.001). We found positive correlations between serum AOPP concentrations and total fibroids weight (r=0.339; p=0.028), serum AOPP and serum protein carbonyls with duration of infertility (r=0.762; p=0.006 and r=0.683; p=0.021, respectively).
This study, for the first time, reveals a significant increase of protein oxidative stress status and reduced antioxidant capacity in sera from women with uterine leiomyoma.
To investigate whether the controversy about fluctuations of anti-Müllerian hormone (AMH) levels during the menstrual cycle results from differences between the immunoassays currently available: the ...Beckman Coulter Immunotech kit (Fullerton, CA) and the Diagnostic Systems Laboratories kit (Webster, TX).
Prospective trial.
Fertility clinics of two tertiary university hospitals.
One hundred sixty-eight blood samples from three different populations. Serial samples at set intervals from the LH surge were taken in a fourth population of 10 volunteers.
We remeasured AMH levels by using the Diagnostic Systems Laboratories kit in 168 blood samples in which AMH initially had been measured by using the Beckman Coulter assay. We also conducted serial AMH measurements (n = 7) during the menstrual cycle of 10 women.
Linear regression of AMH levels determined by using 2 different assays and analysis of variance of serial measurements in the menstrual cycle.
We found a linear relationship between the 2 methods, with a correlation coefficient of 0.88. When repeated individual AMH measures were longitudinally analyzed in relation to the LH surge, a slight but significant decrease was observed after ovulation.
Differences in AMH fluctuations during the menstrual cycle reported in recent publications do not result from the use of different AMH assays. The changes in AMH levels after ovulation are slight, yet statistically significant. However, the fluctuations observed are smaller than intercycle variability and therefore are not clinically relevant as far as AMH measurements for clinical purposes are concerned. In daily practice, AMH therefore can be measured anytime during the menstrual cycle.
To evaluate the rate of intrinsic ureteral endometriosis in patients presenting with severe ureteral endometriosis.
Observational study between June 1992 and December 2007.
University tertiary ...referral center.
Twenty-nine patients presenting deeply infiltrating endometriosis (DIE) with severe ureteral endometriosis. Severe ureteral endometriosis was defined as DIE lesions causing significant obstruction to the urinary flow with ureteral stenosis.
Complete surgical exeresis of DIE lesions.
Pre- and peroperative evaluation associated with histologic analysis. Intrinsic ureteral endometriosis was defined as presence of DIE lesions infiltrating the ureteral muscularis.
In a series of 627 patients with histologic proved DIE, we observed 29 (4.6%) patients with severe ureteral endometriosis. Ureteral lesions (n = 34) were right sided in 7 (24.1%) patients, left sided in 17 (58.6%) patients, and bilateral in 5 (17.3%) patients. Eleven (37.9%) patients presented intrinsic lesions. Out of the 34 ureteral lesions 13 (38.2%) were intrinsic. In cases of radical ureteral surgery (n = 21 patients; n = 24 ureteral lesions) intrinsic ureteral DIE was observed in 52.4% (11 cases) of the patients and in 54.2% (13 cases) of the ureteral lesions.
The prevalence of intrinsic ureteral endometriosis is underestimated. This result must be taken into account when specifying the surgical modalities for patients presenting with severe ureteral endometriosis.
To analyze the lymph node involvement by endometriotic foci in rectosigmoid endometriosis and to correlate it with clinical and histological parameters including the presence of lymphovascular ...invasions, which could explain this lymph node involvement.
A prospective study of 26 consecutive cases of rectosigmoid endometriosis between January 2005 and January 2007.
A multidisciplinary study including clinical and pathological data.
Twenty-six patients with symptomatic rectosigmoid endometriosis.
Laparoscopic surgery with pathological analysis of each specimen.
Involvement of lymph nodes by endometriotic foci was correlated with the size and the wall layers affected by endometriotic lesions, the number of lymph nodes retrieved, and the presence of lymphovascular invasions demonstrated by D2-40, a specific antibody to lymphatic vessels.
Lymph node involvement by endometriosis was observed in 11 of the 26 patients (42.3%) and correlated with the size of the lesions, the number of lymph nodes retrieved, and the presence of lymphovascular invasions, which were observed in 36.3% of cases.
Our data confirm that lymph node involvement by endometriotic foci is a frequent event in rectosigmoid endometriosis and may result at least partially from a lymphatic spread of the disease.
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