Adrenocorticotrophic hormone exerts marked lipid-lowering effects in simvastatin-treated patients

OBJECTIVE: Recently, it was reported that treatment with adrenocorticotrophic hormone (ACTH) has a strong lipid-lowering effect in healthy individuals. The mechanism behind this has not been established. The aim of the present investigation was to study the effect of ACTH on the plasma lipoprotein pattern in patients treated with a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor. DESIGN: The ACTH treatment was given to 10 patients who were on long-term treatment with simvastatin 40 mg daily. ACTHI-24 was administered at the dose of 1 mg daily for four consecutive days. Blood samples for analyses of lipids, lipoproteins and apolipoproteins were collected before and after treatment. Second baseline was obtained 2 weeks after the end of treatment. RESULTS: The serum concentrations of cholesterol, triglycerides, low density lipoprotein (LDL) cholesterol, apolipoprotein B and lipoprotein(a) fell significantly by 16, 23, 23, 10 and 38%, respectively. The serum apolipoprotein E concentration increased significantly by 39%; the fraction that was not associated with apolipoprotein B increased by 47% whereas the fraction that was did not change significantly. There were no changes in the serum concentrations of high density lipoprotein (HDL) cholesterol and apolipoprotein AI. At the second baseline, the lipid variables had generally returned to previous levels. CONCLUSIONS: In patients on long-term simvastatin treatment, ACTH had marked lowering effects on the lipoproteins that contain apolipoprotein B. Moreover, the serum apolipoprotein E concentration increased significantly in response to ACTH treatment.     

Receiver operating characteristic (ROC) analysis of day 5 morphology grading and metabolomic Viability Score on predicting implantation outcome

Purpose

Assessment of embryo viability is a key component of in vitro fertilization (IVF) and currently relies largely on embryo morphology and cleavage rate. In this study, we used receiver operating characteristic (ROC) analysis to compare the Viability Score (generated by metabolomic profiling of spent embryo culture media using near infrared (NIR) spectroscopy) to morphologic grading for predicting pregnancy in women undergoing single embryo transfer (SET) on day 5.

Methods

A total of 198 spent embryo culture media samples were collected in four IVF centers located in the USA, Europe and Australia. First, 137 samples (training set) were analyzed by NIR to develop an algorithm that generates a Viability Score predictive of pregnancy for each sample. Next, 61 samples (validation set) were analyzed by observers blinded to embryo morphology and IVF outcome, using the Day 5 algorithm generated with the training set. Pregnancy was defined as fetal cardiac activity (FCA) at 12 weeks of gestation.

Results

The Area Under the Curve (AUC) was greater for the metabolomic Viability Score compared to Morphology [Training set: 0.75 versus 0.55, p = 0.0011; Validation set: 0.68 versus 0.50, P = 0.021], and for a Composite score (obtained using a model combining Viability Score with morphologic grading), compared to morphology alone [0.74 versus 0.50, p = 0.004].

Conclusions

Our findings suggest that Viability Score alone or in combination with morphologic grading has the potential to be a better classifier for pregnancy outcome than morphology alone in women undergoing SET on day 5.