This study compares the effects of glucose and fatty acid on hepatic lipid synthesis and apolipoproteln (apo) B secretion. To do so, varying concentrations of either glucose or oleic acid were added to the medium in which HepG2 cells were being incubated. Intracellular triacylglycerol and cholesteryl ester synthesis and secretion were measured by addition of radioisotopic tracers and by determination of mass, whereas apo B concentration in the medium was measured by a specific enzyme-linked immunosorbent assay. The data indicate that increasing concentrations of glucose in the medium resulted in increased synthesis of triacylglycerol within the cell and increased secretion of triacylglycerol into the medium. Apo B secretion into the medium, however, did not change, and intracellular synthesis and secretion of cholesteryl ester did not change as well. By contrast, addition of oleic acid to the medium resulted in increased synthesis and secretion of both cholesteryl ester and triacylglycerol, and this was associated with increased secretion of apo B into the medium. Thus, a carbohydrate load resulted in secretion of normal numbers of triacylgtycerol-enriched apo B particles by this hepatocyte cell line, whereas a fatty acid load led to the secretion of increased numbers of apo B particles, which were essentially normal in composition. 1 -2 It is obviously, therefore, not a unitary entity. Two different clearance defects have been recognized: the first involves the rate of triacylglycerol hydrolysis (lipoprotein lipase and apolipoprotein [apo] CH deficiency fall in this category 1 ), whereas the second involves impaired removal of chylomicron and very low density lipoprotein (VLDL) remnants (with type III hyperlipoproteinemia being the prototype of this class of disorders).3 Two different genetic forms of hepatic overproduction of VLDL have also been recognized: familial hypertriglyceridemia and familial combined hyperlipidemia. The former is characterized by the secretion of normal numbers of triacylglycerol-enriched VLDL particles, whereas the latter is characterized by secretion of increased numbers of VLDL particles of normal composition. 4 -6 However, little is yet known of the processes that regulate VLDL secretion. Almost all available in vitro evidence supports the view that apo B production rates are modulated by posttranslational mechanisms, 7 -8 and we have advanced the hypothesis that cholesteryl ester synthesis is critical in this regard, at least so far as the response to increased delivery of fatty acids to the liver is concerned. 9 Nevertheless, it has been well documented that carbohydrate feeding also can lead to increased plasma triacylglycerols, 1011 presumably through increased delivery of glucose to the liver. Accordingly, the present studies were undertaken to compare the response of HepG2 cells on the one hand to an exogenous glucose load and, on the other, to an exogenous fatty acid load. Our expectation was that the latter would result in secretion of increased numbers of apo B partic...

Objective: To compare the influence of dual suppression with the use of GnRH agonist plus aromatase inhibitor compared with suppression with the use of GnRH agonist alone or no suppression at all in patients with idiopathic recurrent implantation failure (RIF). Design: Retrospective cohort study. Setting: University-affiliated reproductive center. Patient(s): A total of 523 infertile women who failed two blastocyst transfers underwent a third frozen blastocyst transfer. Women with known endometriosis were excluded. Intervention(s): A total of 204 subjects were not pretreated, 143 received 2 months of GnRH agonist (3.75 mg intramuscular leuprolide acetate monthly) only, and 176 received GnRH agonist and aromatase inhibitor (5 mg oral letrozole daily for 60 days). Demographic and stimulation information was collected and cycle outcomes reported. Main Outcome Measure(s): Clinical pregnancy rates. Result(s): Age, antral follicle count, basal FSH levels, duration of infertility, previous pregnancies, and full-term deliveries were similar (P>.05). Clinical pregnancy rates were higher among women who received GnRH agonist plus letrozole compared with women who received GnRH agonist only or women without pretreatment (63%, 42%, and 40%, respectively; P< .0001). Live birth rates were higher among women who received GnRH agonist plus letrozole compared with the other groups (56%, 36%, and 34%; P< .0001). No differences in pregnancy outcomes were noted between patients who did not receive pretreatment and those in the GnRH agonist only group. Conclusion(s):In patients with RIF, treatment with a GnRH agonist plus letrozole may improve live birth rates in subsequent cycles. We hypothesize that this improvement is due to alterations in the endometrium receptivity or treatment of undiagnosed endometriosis. (Fertil Steril Ò 2019;112:98-104. Ó2019 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.