Serum Vitamin D status is associated with increased blastocyst development rate in women undergoing IVF.

RESEARCH QUESTION: To determine the relationship between vitamin D (VitD) status and embryological, clinical pregnancy and live birth outcomes in women undergoing IVF. DESIGN: Cross-sectional, observational study conducted at a university-affiliated private IVF clinic. A total of 287 women underwent 287 IVF cycles and received a fresh embryo transfer. Patients had their serum 25-hydroxyvitamin D2/D3 (VitD) determined on the day of oocyte retrieval, which was analysed in relation to blastocyst development rate, clinical pregnancy and live birth outcomes. RESULTS: In stepwise, multivariable logistic regression models, increases in blastocyst development rate, number and quality, along with embryo cryopreservation and utilization rates were associated with women with a sufficient VitD status (≥20 ng/ml). For a single increase in the number of blastocysts generated per cycle or embryos cryopreserved per cycle, the likelihood for the patient to be VitD sufficient was increased by 32% (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.10-1.58, P = 0.002 and OR 1.33, 95% CI 1.10-1.60, P = 0.004, respectively). Clinical pregnancy (40.7% versus 30.8%, P = 0.086) and live birth rates (32.9% versus 25.8%, P = 0.195) in the sufficient VitD group versus the insufficient group were not significantly different and VitD sufficiency was not significantly associated with these outcomes. CONCLUSION: A strong relationship was observed between blastocyst development and VitD sufficiency. However, there was no association between VitD and clinical pregnancy or live birth outcomes. Further larger studies are needed to investigate whether the observed effect on blastocyst development may have downstream implications on subsequent clinical pregnancy or live birth rates, and on a potential mechanism where sufficient VitD concentrations are linked to improved IVF outcomes.

Method Protocols for Metabolic and Functional Analysis of the BRIN-BD11 ß-Cell Line: A Preclinical Model for Type 2 Diabetes.

In type 2 diabetes, prolonged dysregulation of signalling and ß-cell metabolic control leads to ß-cell dysfunction, and is increasingly associated with abnormal metabolic states which disrupt normal cellular physiology. Utilization of appropriate ß-cell models enables a systematic approach to understand the impact of perturbations to the biological system. The BRIN-BD11 ß-cell line is a useful, pre-clinical cell model for ß-cell dysfunction associated with type 2 diabetes, among other metabolic disorders. The present chapter describes detection and analysis of ß-cell dysfunction with respect to changes in bioenergetics and metabolism, generation of intracellular reactive oxygen species, and acute and chronic insulin secretion in the BRIN-BD11 cell line.

Live birth rates are satisfactory following multiple IVF treatment cycles in poor prognosis patients.

This seven-year retrospective study analysed the live birth rate (LBR) for women undergoing IVF treatment with various antral follicle counts (AFC). The LBR decreased with lower AFC ratings, and in 290 treatment cycles for women in the poorest AFC category, ≤4 follicles (group E), the LBR was the lowest at 10.7%. The pregnancy loss rate (PLR) significantly increased with poorer AFC categories, from 21.8% in AFC group A (≥20 follicles), to 54.4% in AFC group E (p<0.0001). This trend was repeated with advancing age, from 21.6% for younger women (<35years), to 32.9, 48.5 and 100% for ages 35-39, 40-44 and ≥45 years, respectively (p<0.0001). However, LBR within the specific AFC group E cohort was also age-dependent and decreased significantly from 30.0% for <35 years old, to 13.3, 3.9 and 0% for patients aged 35-39, 40-44 and ≥45 years, respectively. Most, importantly, LBR rates within these age groups were not dependent on the number of IVF attempts (1st, 2nd, 3rd or ≥4 cycles), which indicated that cycle number should not be the primary deciding factor for cessation of IVF treatment in responding women <45years old.

Pigment epithelium-derived factor (PEDF) regulates metabolism and insulin secretion from a clonal rat pancreatic beta cell line BRIN-BD11 and mouse islets.

Pigment epithelium-derived factor (PEDF) is a multifunctional glycoprotein, associated with lipid catabolism and insulin resistance. In the present study, PEDF increased chronic and acute insulin secretion in a clonal rat ß-cell line BRIN-BD11, without alteration of glucose consumption. PEDF also stimulated insulin secretion from primary mouse islets. Seahorse flux analysis demonstrated that PEDF did not change mitochondrial respiration and glycolytic function. The cytosolic presence of the putative PEDF receptor - adipose triglyceride lipase (ATGL) - was identified, and ATGL associated stimulation of glycerol release was robustly enhanced by PEDF, while intracellular ATP levels increased. Addition of palmitate or ex vivo stimulation with inflammatory mediators induced ß-cell dysfunction, effects not altered by the addition of PEDF. In conclusion, PEDF increased insulin secretion in BRIN-BD11 and islet cells, but had no impact on glucose metabolism. Thus elevated lipolysis and enhanced fatty acid availability may impact insulin secretion following PEDF receptor (ATGL) stimulation.