In order to evaluate the involvement of cell proliferation and apoptosis in the pathogenesis of endometriosis, we investigated the effects of interferon-gamma (IFN-gamma) on cell growth inhibition and apoptosis of cultured ovarian endometriotic cyst stromal cells (ECSC), eutopic endometrial stromal cells with endometriosis (ESCwE) and normal endometrial stromal cells (NESC) by modified methylthiazoletetrazolium assay, 5-bromo-2'-deoxyuridine incorporation assay and internucleosomal DNA fragmentation assay. The expression of apoptosis-related molecules and IFN-gamma receptor 1 was also examined in ECSC, ESCwE and NESC using western blot analysis. IFN-gamma significantly inhibited cell proliferation and DNA synthesis of ESCwE and NESC, and induced apoptosis of these cells. In contrast, IFN-gamma did not show apparent effects on the viable cell number, DNA synthesis, or apoptosis of ECSC. An up-regulated expression of Bcl-2 and Bcl-X(L) proteins was observed in ECSC in comparison with ESCwE and NESC, whereas the levels of Bax, Bad, Fas and Fas ligand proteins in ECSC were similar to those in ESCwE and NESC. IFN-gamma receptor 1 expression was detected in ECSC, ESCwE and NESC. Enhanced expression of anti-apoptotic molecules in the ectopic endometrial cells may contribute to the development of endometriosis by conferring resistance to cytokine-induced apoptosis and increasing the chance that these cells will survive and implant outside the uterus. Further investigations on the regulation of cell proliferation in both the endometriotic and the normal endometrium may be important for the elucidation of the pathogenesis of endometriosis.
Problem What are the pregnancy outcomes after the OPtimization of Thyroid function, Immunity, and Uterine Milieu (OPTIMUM) treatment strategy in patients with repeated implantation failure (RIF)? Method of study Infertile women with a history of RIF after more than three embryo transfer (ET) cycles underwent implantation testing, including a hysteroscopy, endometrial biopsy for CD138 immunostaining and bacterial culture, and serum 25‐hydroxyvitamin D3, interferon‐γ‐producing helper T (Th1) cell, IL‐4‐producing helper T (Th2) cell, thyroid‐stimulating hormone, thyroid peroxidase antibody, and thrombophilia screening between April 2017 and August 2018. We treated chronic endometritis with antibiotics, aberrant high Th1/Th2 cell ratios with vitamin D and/or tacrolimus intake, overt/subclinical hypothyroidism with levothyroxine, and thrombophilia with low‐dose aspirin. Of the 116 RIF women, 88 women with 133 ET cycles were recruited from a questionnaire‐based survey regarding pregnancy outcomes. Fifty‐nine consecutive RIF patients without the OPTIMUM treatment strategy were also recruited as a control. Results The 116 women with RIF after the OPTIMUM treatment strategy were 38.3 ± 3.8 years old and had an implantation failure history over 5 (3‐19) ET cycles. Implantation testing identified impaired intrauterine circumstances in 75 women (64.7%), an aberrant elevated Th1/Th2 cell ratio in 56 women (48.3%), and thyroid abnormalities in 33 women (28.4%). Cumulative ongoing pregnancy rates including spontaneous pregnancy in the patients aged < 40 and ≥ 40 years were 72.7% and 45.5% within two ET cycles, respectively. The pregnancy outcomes in the OPTIMUM group were significantly higher than those in the control. Conclusions The OPTIMUM treatment strategy improved pregnancy outcomes in patients with RIF.
To evaluate the involvement of chemokines in the pathogenesis of endometriosis, we investigated the expression of CXC chemokines in cultured ovarian endometriotic cyst stromal cells (ECSC), endometrial stromal cells with endometriosis (ESCwE), and normal endometrial stromal cells (NESC). Using ELISA, TNF-alpha significantly enhanced the production of IL-8, growth-related oncogene alpha, and epithelial neutrophil-activating peptide-78 in all cases of ECSC (n = 10), ESCwE (n = 6), and, NESC (n = 10). IL-1beta did not affect the production of these chemokines in eight of 10 cases of ECSC. In contrast, IL-1beta significantly enhanced the expression of these chemokines in all cases of ESCwE (n = 6) and NESC (n = 10). Western blot analysis revealed down-regulation of expression of IL-1 receptor type 1 (IL-1-R1) in all cases of ECSC with low response to IL-1beta (n = 8). In contrast, significant IL-1-R1 expression was detected in all cases of NESC. Although IL-1-R1 expression was detected in all cases of ESCwE (n = 6), its expression in ESCwE tended to decrease compared with that in NESC. Moreover, phosphorylation of inhibitor kappaB-alpha was detected in all cases of ESCwE and NESC after stimulation with IL-1beta, but not in ECSC with low response to IL-1beta (n = 8). In contrast, significant IL-1-R2 expression was detected in all cases of ECSC, ESCwE, and NESC. The present findings suggest that the dysregulation of IL-1/IL-1-R system relates to immunological dysfunction in endometriosis. The alteration of the CXC chemokines expression may be important for elucidation of the pathogenesis of endometriosis.
Objective: To examine the absolute and relative changes in skeletal muscle (SM) size using whole body magnetic resonance imaging (MRI) in response to heavy resistance training (RT). Method: Three young men trained three days a week for 16 weeks. Results: MRI measured total SM mass and fat free mass (FFM) had increased by 4.2 kg and 2.6 kg respectively after resistance training. Conclusions: RT induces larger increases in SM mass than in FFM. RT induced muscle hypertrophy does not occur uniformly throughout each individual muscle or region of the body. Therefore the distribution of muscle hypertrophy and total SM mass are important for evaluating the effects of total body RT on muscle size.A ccurate measurements of skeletal muscle (SM) mass and distribution in humans are important for studies of SM hypertrophy response to heavy resistance training (RT). Currently, the most accurate in vivo methods of measuring SM mass are multiscan magnetic resonance imaging (MRI) and computed tomography.1 Despite its safety, most MRI studies have only evaluated regional-for example, arms, trunk, and legs-SM mass. 1 We recently reported whole body MRI using a contiguous slice by slice (no interslice gap) method to evaluate total SM mass and its distribution.2 Using this approach, the distribution of RT induced whole body SM hypertrophy can be investigated.To date, most studies 3 4 have only evaluated limb muscle hypertrophy, and very few have reported RT induced muscle hypertrophy in the trunk region.5 More importantly, the distribution of the relative increases in RT induced muscle hypertrophy has not been reported. Thus the purpose of this pilot study was to examine the absolute and relative changes in SM size using contiguous whole body MRI scans in response to RT. METHODSThree healthy young men (age 20-21 years) volunteered for the study. All were physically active, but none had participated in RT before the start of the programme. All subjects signed informed consent documents. The department's ethical commission approved the study.RT was carried out three days a week for 16 weeks. Three lower body (squat, knee extension, and knee flexion) and two upper body (bench press and latissimus dorsi pull down) exercises were performed. Workouts consisted of a warm up set followed by three sets to failure of 8-12 repetitions for each of the five exercises. The loads were progressively increased to maintain this range of repetitions per set. One repetition maximum (1RM) strength was determined by progressively increasing the weight lifted until the subject failed to lift the weight through a full rage of motion. Strength of the squat was assessed using the 3RM test.Total body SM distribution and mass were measured using an MRI 1.5-T scanner (GE Signa, Milwaukee, Wisconsin, USA) with spin echo sequence (TR, 1500 milliseconds; TE, 17 milliseconds).2 Contiguous transverse images with 1.0 cm slice thickness (no interslice gap) were obtained from the first cervical vertebra to the ankle joints for each subject. Four sets extended from the...
STUDY QUESTION Are there any differences in live birth rates (LBR) following fresh blastocyst transfer in natural or clomiphene-stimulated cycles, or after elective blastocyst freezing in clomiphene-stimulated cycles followed by thawing and transfer at different time-points? SUMMARY ANSWER Clomiphene citrate (CC) administration adversely affected the LBR after single fresh blastocyst transfer (SBT) in CC cycles compared with that in natural cycles, while this adverse effect of CC is not present when a single vitrified-warmed blastocyst transfer (SVBT) is performed in subsequent natural ovulatory cycles, regardless of the duration between CC administration and the day of SVBT. WHAT IS KNOWN ALREADY CC affects uterine receptivity associated with a thinning of the uterine endometrium through an antioestrogenic effect. However, the duration that this adverse effect of CC on uterine endometrium persists after initial use is still unknown. STUDY DESIGN, SIZE, DURATION A retrospective cohort study of 157 natural cycle IVFs followed by SBT and 1496 minimal ovarian stimulation with CC IVF cycles followed by SBT ( n = 24) or SVBT ( n = 1472) from January 2010 to December 2014 was conducted. SVBT cycles were classified into two groups according to the period between the last day of CC administration and the day of SVBT (A: ≤60 d and B: ≥61 d). All groups were then compared based on pregnancy outcomes (natural-SBT group: n = 157, CC-SBT group: n = 24, SVBT-A: n = 1143, SVBT-B: n = 329). PARTICIPANTS/MATERIALS, SETTING, METHODS Women were aged 30–39 years at oocyte retrieval. In SVBT cycles, blastocysts were vitrified and warmed using a Cryotop safety kit. SVBT was performed in subsequent natural ovulatory cycles. The main outcomes were LBR and neonatal outcome, and both were compared among the groups. MAIN RESULTS AND THE ROLE OF CHANCE The LBR in the CC-SBT group (29.2%, 7/24) was significantly lower compared with the natural-SBT (56.1%, 88/157) ( P = 0.01) and SVBT-A (50.0%, 572/1143) ( P = 0.04), but not SVBT-B (47.4%, 156/329), groups. Furthermore, multivariate logistic regression analysis revealed that the LBR was comparable among the natural-SBT and SVBT groups, but was significantly lower in the CC-SBT group (adjusted odds ratio: 0.324, 95% CI: 0.119–0.800, P = 0.01). No significant differences among all groups were observed for gestational age ( P = 0.19), birthweight ( P = 0.41) and incidence of malformation ( P = 0.53). LIMITATIONS, REASONS FOR CAUTION In this study we analysed a biased sampl...
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