Systematic review and network meta-analysis of hydrosalpinx treatment before in vitro fertilization.

OBJECTIVES: To compare different methods to treat hydrosalpinx, based on both ablative and non-ablative approaches, in infertile patients before undergoing IVF-ET. METHODS: Systematic review and network meta-analysis (NMA) of comparisons between different treatments of hydrosalpinx in infertile patients undergoing IVF. DATA SOURCES: structured searches in common citation databases. Study inclusion criteria: peer-reviewed randomized trials (RCT) or cohort studies comparing effects of salpingectomy, laparoscopic proximal tubal occlusion (LTO), insertion of intratubal device (ITD), sclerotherapy, ultrasound-guided aspiration and no treatment, on live birth, ongoing pregnancy, clinical pregnancy as main outcomes, considering also miscarriage, ectopic pregnancy and complications as secondary outcomes. Principal NMA included RCT, and aggregated NMA of RCT and observational studies was carried out. Pooled effects have been estimated by Odds Ratio (OR) and its 95% confidence interval (CI) for direct and indirect-mixed comparisons, derived from random-effects models. Imprecision and heterogeneity of NMA estimations was assessed by comparison of its 95% CI with predefined intervals for clinically relevant size of effect (OR <0.9 or >1.1). Surface under the cumulative ranking curve (SUCRA) were used to predict treatment rankings for each outcome. RESULTS: Nine RCT were included in main analysis, plus 17 additional observational studies in additional analysis. NMA of RCT did not identify significant differences in the effect of compared treatments on live birth rate, and LTO was the option with the highest value of SUCRA (0.92, mean rank: 1.2). Salpingectomy and US-aspiration associated to a significant increase of ongoing pregnancy rate compared to no treatment, according to NMA results (NMA OR: 4.35; 95% CI: 1.7, 11.14 and 2.8; 95% CI: 1.03, 7.58 respectively). Salpingectomy had the highest SUCRA value (0.88, mean rank: 1.4). NMA estimated significant increase of clinical pregnancy rate for salpingectomy compared with no treatment (NMA OR: 2.24; 95% CI: 1.3, 3.86) as well as for LTO versus no treatment (NMA OR: 2.55; 95% CI: 1.2, 5.41). Both comparisons were affected by a high grade of heterogeneity. For clinical pregnancy, LTO was the intervention with highest SUCRA (0.85; mean rank: 1.6). Regarding secondary outcomes, feasible NMA estimates did not support significant differences between treatments effects. According to aggregated NMA including randomized and observational studies, sclerotherapy showed significant beneficial effects on live birth rate compared to no treatment (NMA (OR: 4.6; 95% CI: 1.21, 17.46). Compared with untreated patients, the aggregated NMA estimates a higher ongoing pregnancy rate in patients treated with salpingectomy (NMA OR: 3.35; 95% CI: 2.12, 5.12), US-aspiration (NMA OR: 2.16; 95% CI: 1.28, 3.65) and LTO (NMA OR: 2.46; 95% CI: 1.11, 5.43). Salpingectomy and LTO produced a higher beneficial effect compared to ITD, based on both direct and indirect comparisons. Salpingectomy obtained the highest SUCRA value in rank of effects on ongoing pregnancy (0.94; mean rank: 1.2). NMA found significant effects on clinical pregnancy for comparisons between the different active management procedures compared with no treatments, with the exception of ITD insertion. LTO had more increasing effect on clinical pregnancy rate compared with US-aspiration (NMA OR: 2.04; 95% CI: 1.05, 3.97), while for the rest of the comparisons between procedures no significant differences were identified. NMA ranked LTO as the treatment with a highest SUCRA value (0.91; mean rank: 1.5). NMA prediction models identified LTO as best intervention to reduce miscarriage (SUCRA value: 0.84; mean rank: 1.8), as sclerotherapy as safer option in terms of ovarian response to IVF stimulation. CONCLUSIONS: The present NMA fails to support the effectiveness of any option to treat hydrosalpinx before IVF in order to improve live birth rates, although the beneficial effect of salpingectomy and US aspirations on ongoing pregnancy rates and of both salpingectomy and LTO on clinical pregnancy rates emerges from our analysis, which reinforces current recommendations. Based on the aggregated analyses, sclerotherapy could be a promising alternative to conventional laparoscopic techniques, combined with a favorable safety profile. This article is protected by copyright. All rights reserved.

Considerations for the development of guidance on dose level selection for developmental and reproductive toxicity studies.

In 2022, the European Chemicals Agency issued advice on the selection of high dose levels for developmental and reproductive toxicity (DART) studies indicating that the highest dose tested should aim to induce clear evidence of reproductive toxicity without excessive toxicity and severe suffering in parental animals. In addition, a recent publication advocated that a 10% decrease in body weight gain should be replaced with a 10% decrease in bodyweight as a criterion for dose adequacy. Experts from the European Centre for Ecotoxicology and Toxicology of Chemicals evaluated these recent developments and their potential impact on study outcomes and interpretation and identified that the advice was not aligned with OECD test guidelines or with humane endpoints guidance. Furthermore, data analysis from DART studies indicated that a 10% decrease in maternal body weight during gestation equates to a 25% decrease in body weight gain, which differs from the consensus of experts at a 2010 ILSI/HESI workshop. Dose selection should be based on a biological approach that considers a range of other factors. Excessive dose levels that cause frank toxicity and overwhelm homeostasis should be avoided as they can give rise to effects that are not relevant to human health assessments.

Impact of congenital uterine anomalies on obstetric and perinatal outcomes: systematic review and meta-analysis.

Background: Congenital uterine anomalies (CUA) can be associated with impairments of early and late pregnancy events. Objective: To assess the impact of CUA on reproductive outcomes in pregnancies conceived spontaneously or after assisted reproduction. Materials and Methods: Systematic review and meta-analysis of cohort studies comparing patients with CUA versus women with normal uterus. A structured literature search was performed in leading scientific databases to identify prospective and retrospective studies. The Newcastle-Ottawa scale, adapted to AHRQ standards, was used to assess the risk of bias. Pooled odds ratios (OR) were calculated. Publication bias and statistical heterogeneity were assessed, and meta-regression was used to analyse the heterogeneity. Main outcome measures: Miscarriage, ectopic pregnancy, placental abruption, term, and premature rupture of membranes (PROM), malpresentation at delivery, preterm delivery prior to 37, 34 and 32 weeks, caesarean delivery, intrauterine growth restriction/small for gestational age, foetal mortality and perinatal mortality. Results: 32 studies were included. CUAs increased significantly the risk of first/second trimester miscarriage (OR:1.54;95%CI:1.14-2.07), placental abruption (OR:5.04;3.60-7.04), PROM (OR:1.71;1.34-2.18), foetal malpresentation at delivery (OR:21.04;10.95-40.44), preterm birth (adjusted OR:4.34;3.59-5.21), a caesarean delivery (adjusted OR:7.69;4.17-14.29), intrauterine growth restriction/small for gestational age (adjusted OR:50;6.11-424), foetal mortality (OR:2.07;1.56-2.73) and perinatal mortality (OR:3.28;2.01-5.36). Conclusions: CUA increases the risk of complications during pregnancy, delivery, and postpartum. Complications most frequent in CUA patients were preterm delivery, foetal malpresentation, and caesarean delivery. What is new?: Bicornuate uterus was associated with the highest number of adverse outcomes, followed by didelphys, subseptate and septate uterus.

Tejido adiposo como órgano endocrino / Adipose tissue as an endocrine organ

Obesity is a condition in which there is excessive accumulation of subcutaneous and abdominal adipose tissue. This adipose tissue is no longer considered inert and dedicated solely to energy storage. For more than a decade is considered in an active tissue in the regulation of physiological and pathological processes, including immunity and inflammation. Adipose tissue produces and releases a variety of adipokines (leptin, adiponectin, resistin, and visfatin) and cytokine pro - and anti -inflammatory (TNF - alpha 945;, IL-4, IL-6, etc.). Adipose tissue is also implicated in the development of chronic metabolic diseases such as type 2 diabetes or cardiovascular disease. Obesity is therefore an under lying condition for the appearance of inflammatory and metabolic diseases. These adipokines, behave, according to each physiological state, such as a metabolic disrupter. The environment (diet and sedentary lifestyle) have significantly changed the constitution of this adipose tissue, so that patterns of good nutrition and lifestyle play a critical role in the growth of the adipose tissue...

Marcadores de inflamación y autoinmunidad en pacientes con diabetes tipo 1 / And inflammation markers in patients with diabetes autoimmunity type 1

To determine the serological levels of inflammatory markers and autoimmunity in patients with T1D compared with controls, and determined its relation to the duration of diabetes. Methods: We selected 139 patients with T1D without chronic complications of diabetes, and 110 control subjects without family history of diabetes. Serological ultrasensitive C-reactive protein levels (usCRP), interleukin- 6 and adhesion protein VCAM through ELISA assay were determined. Autoimmune profile was also analyzed through GAD65, IA-2 and ZnT8 autoantibodies. Results: Increased levels of usCRP 1.74 (0.10 to 13.6) vs 1.08 (0.40 to 3.70) ng/ml (p < 0.03), VCAM 236.0 (122.2 to 693.5) vs 185.4 (101.3 to 421.3) ng/ml, p < 0.02 and IL-6 1.73 (0.40 to 9.10) vs 1.28 (0.30 to 4.60) ng/ml, p < 0.05 was found in the group of T1D patients compared with the control group. When analyzing inflammatory markers according to age groups (0-10 years and > 10 years), the values of usCRP were higher in the second group. There was no significant association between patients with DM1 and autoimmune positive profile with a higher frequency of markers of inflammation. Conclusions: These results suggest the presence of pro-inflammatory state is considerably more frequent in patients with T1D. The increased level of usCRP and IL -6 and according to age of the patients could indicate a possible role of adiposity and weight gain during the adolescence in the higher frequency of inflammatory markers in T1D patients...

The petrosal ganglion of the adult cat: neuronal count, sectional area, and their respective distributions

The petrosal ganglion contains most of the perikarya of sensory neurons of the glossopharyngeal nerve. We studied the number and size of neuronal somata in 4 petrosal ganglia from adult cats. Ganglia were serially sectioned in length at 8 microns, sections drawn through a projection microscope, and those neuronal profiles presenting nuclei and nucleoli on each section were counted and their areas measured. The number of neurons ranged from 2311 to 3429 (2908 +/- 271; mean +/- SEM). Neurons were symmetrically distributed around the longitudinal axes of most ganglia, with a skewed distribution in only one ganglion. The sectional area of most neurons (> 98 percent) ranged between 250 and 1725 microns 2, with median values of 667-963 microns 2. Area distributions were significantly different, but differences never exceeded 8.2 percent in related area bins. The ganglion presenting a skewed count distribution and the highest median area departed from the rest, with differences surpassing 25 percent. We conclude that the neuronal population of the petrosal ganglion of the cat is regular both with respect to the number and the size of its constituents, with departures from this pattern probably reflecting individual variations

Folic acid supplementation does not prevent ribavirin-induced anemia

Treatment of chronic hepatitis C consists of inteferon plus ribavirin. The major adverse effect of ribavirin is hemolytic anemia, a complication that limits therapy. Folic acid supplementation is used to improve erythropoiesis in chronic hemolytic anemia. The aim of this study was to evaluate the effectiveness of folic acid supplementation in the prevention of ribavirin-induced anemia in patients being treated for hepatitis C. Twenty one patients enrolled in treatment protocols for hepatitis C received folic acid 1 mg daily and 22 did not. Groups were similar in age, gender, ribavirin dose and baseline hemoglobin. Folic acid supplementation had no effect in the decrease in hemoglobin or the measured parameters of hemolysis. No difference between males and females was noted for hemoglobin decrease or lowest hemoglobin levels. In our study, folic acid showed no beneficial effect in the prevention of ribavirin-induced anemia.

Response to combination therapy of interferon alfa-2b plus ribavirin in Hispanics with chronic hepatitis C

OBJECTIVE: To evaluate the response rate of Hispanics with chronic hepatitis C to combination therapy of interferon alfa-2b plus ribavirin and to assess its adverse events. BACKGROUND: Hepatitis C virus may lead to chronic infection and multiple complications. Response to combination therapy of interferon plus ribavirin has been studied in many populations. African Americans have been found to have a lower response rate than Caucasians. However, little data exist for Hispanics. METHODS: Hispanic patients from Puerto Rico with chronic hepatitis C were eligible for the study between November 1997 and February 2000. The Institutional Review Boards of the participating institutions approved the study. Written informed consents were obtained. Combination therapy was given for 48 weeks and patients were followed for 24 weeks after treatment. Analysis of response to therapy was performed in an intention-to-treat basis. RESULTS: The most frequent adverse event was anemia (89%), associated to ribavirin. Sustained response was 23% for naive patients, 45% for relapsers, and 8% for non-responders to previous interferon monotherapy (p < 0.001). Data to analyze response was not available in 27% of patients. Hispanic patients had a low response rate to combination therapy. CONCLUSIONS: Response rates to combination therapy for Hispanic naive and previously non-responder patients are lower than in other reported populations. This may be due to a high prevalence of genotype 1 in Puerto Rico, which is associated to poor response. The higher response rate of relapsers, similar to those reported previously, was expected since these patients showed a previous response to interferon monotherapy. Ethnic factors may play a role in the response to therapy and should be further studied to determine proper treatment strategies for this population.

Clasificación mapuche y fracasos orgánicos precoces: resultados del estudio multicéntrico / MAPUCHE classification and precocious organic failure results of multicentral study

Se presentan los resultados referentes a la mortalidad en terapia intensiva en función de la determinación de niveles de gravedad MAPUCHE y fracasos orgánicos precoces en el marco del estudio multicéntrico de la SATI. En el mismo se recogieron los datos de dos mil doscientos pacientes provenientes de 22 centros de terapia intensiva de diversos puntos del país. La distribución de los enfermos mostró que la mayoría se hallaba en el nivel II. La mortalidad general fue del 30,9 por ciento y ella se incrementaba significativamente a medida que lo hacían los niveles MAPUCHE, siendo mayor en pacientes clínicos en el nivel I y II. Los subniveles demostraron idéntica correlación con la mortalidad. La presencia de fallas precoces determinó una mortalidad significativamente mayor y el número de las mismas se correlacionó significativamente con la mortalidad. Los resultados muestran la utilidad de los sistemas empleados en la determinación de los niveles de gravedad en pacientes críticos asistidos en centros diferentes. Se recalca la importancia de la realización de estudios multicéntricos para valorar la utilidad de uno o más indicadores