No abstract

Metabolic products of the intestinal microbiome such as trimethylamine N-oxide (TMAO) that accumulate in renal failure (gut-derived uremic toxins, GDUTs) affect atherosclerosis and increase cardiovascular risk. We hypothesized that patients on a Mediterranean diet and those consuming lower amounts of dietary precursors would have lower levels of GDUTs. Patients attending vascular prevention clinics completed a Harvard Food Frequency Questionnaire (FFQ) and had plasma levels of TMAO, p-cresylsulfate, hippuric acid, indoxyl sulfate, p-cresyl glucuronide, phenyl acetyl glutamine, and phenyl sulfate measured by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Carotid plaque burden was measured by ultrasound; CKD-Epi equations were used to estimate the glomerular filtration rate. In total, 276 patients completed the study. Even moderate renal function significantly increased plasma GDUTs, which were significantly associated with higher carotid plaque burden. There was no significant difference in plasma levels of any GDUT associated with a Mediterranean diet score or with intake of dietary precursors. In omnivorous patients with vascular disease, the intake of dietary precursors of intestinal metabolites or adherence to a Mediterranean diet did not change plasma GDUT. Approaches other than diet, such as probiotics and repopulation of the intestinal microbiome, may be required to mitigate the adverse effects of GDUTs.

No abstract

Obesity is associated with altered fatty acid profiles, reduced fertility, and assisted reproductive technology (ART) success. The effects of palmitic acid (PA), oleic acid (OA), and their combination on mouse preimplantation development, endoplasmic reticulum (ER) stress pathway gene expression, lipid droplet formation, and mitochondrial reactive oxygen species (ROS) were characterized. Two-cell stage mouse embryos collected from superovulated and mated CD1 females were placed into culture with KSOMaa medium, or PA alone or in combination with OA for 46 h. PA significantly reduced blastocyst development in a concentration-dependent manner, which was prevented by co-treatment with OA. PA and OA levels in mouse reproductive tracts were assessed by liquid chromatography coupled to mass spectrometry (LC-MS). LC-MS indicated higher concentrations of PA in the mouse oviduct than the uterus. Transcript analysis revealed that PA alone groups had increased ER stress pathway (ATF3, CHOP, and XBP1 splicing) mRNAs, which was alleviated by OA co-treatment. OA co-treatment significantly increased lipid droplet accumulation and significantly decreased mitochondrial ROS from PA treatment alone. PA treatment for only 24 h significantly reduced its impact on blastocyst development from the 2-cell stage. Thus, PA affects ER stress pathway gene expression, lipid droplet accumulation, and mitochondrial ROS in treated preimplantation embryos. These mechanisms may serve to offset free fatty acid exposure effects on preimplantation development, but their protective ability may be overwhelmed by elevated PA.

Objective: To assess the impact of class III obesity on outcomes and complications of transvaginal ultrasound-guided oocyte pickup (OPU). Design: Retrospective cohort study. Setting: Hospital-based fertility clinic. Patient(s): All women undergoing OPU procedures during autologous in vitro fertilization (IVF) and oocyte banking cycles, grouped by patient body mass index (BMI: <25, 25-29.9, 30-34.9, 35-39.9, R40 kg/m 2). Intervention(s): Transvaginal OPU under conscious sedation. Main Outcome Measure(s): Sedation and procedure-related parameters and complications. Result(s): A total of 2,141 OPU procedures in 1,579 patients were analyzed, including 121 OPU procedures in 94 patients with BMI R40 kg/m 2. There was a statistically significant increase in total fentanyl and midazolam doses and procedure duration as BMI increased. Compared with patients with BMI <25 kg/m 2 , those with BMI R40 kg/m 2 were more likely to require additional sedation during the procedure (adjusted odds ratio [aOR] 1.99; 95% confidence interval [CI], 1.14-3.49). The rate of difficult access was 28.9% for procedures with BMI R40 kg/m 2 compared with 5.2% with BMI <25 kg/m 2 (aOR 7.57; 95% CI, 4.66-12.29). The OPU was incomplete due to inaccessible follicles through a transvaginal approach in 18.2% of procedures with BMI R40 kg/m 2 compared with 1.3% with BMI <25 kg/m 2 (aOR 16.94; 95% CI, 8.24-34.84). The rates of sedation and procedure-related complications were low, and none occurred in patients with BMI R40 kg/m 2. Conclusion(s): There was no increased risk of complications for women with class III obesity undergoing OPU with conscious sedation. However, the operator was more likely to encounter difficult access and to incompletely aspirate follicles through a transvaginal approach. (Fertil Steril Rep Ò 2020;1:270-6. Ó2020 by American Society for Reproductive Medicine.