Recent cadmium exposure among male partners may affect oocyte fertilization during in vitro fertilization (IVF)

We recently reported evidence suggesting associations between urine cadmium concentrations, reflecting long-term exposure, measured in 25 female patients (relative risk = 1.41, P = 0.412) and 15 of their male partners (relative risk = 0.19, P = 0.097) and oocyte fertilization in vitro. Blood cadmium concentrations reflect more recent exposure. We here incorporate those measures into our prior data set and employ multivariable log-binomial regression models to generate hypotheses concerning the relative effects of long-term and recent cadmium exposure on oocyte fertilization in vitro. No association is indicated for blood cadmium from women and oocyte fertilization, adjusted for urine cadmium and creatinine, blood lead and mercury, age, race/ethnicity and cigarette smoking (relative risk = 0.88, P = 0.828). However, we suggest an inverse adjusted association between blood cadmium from men and oocyte fertilization (relative risk = 0.66, P = 0.143). These results suggest that consideration of long-term and recent exposures are both important for assessing the effect of partner cadmium levels on oocyte fertilization in vitro

Variability in the components of high-density lipoprotein particles measured in human ovarian follicular fluid: a cross-sectional analysis

ObjectiveTo assess the variability of follicular fluid (FF) high-density lipoprotein (HDL) particle components.DesignCross-sectional design with assessment using two-stage nested analysis of variance.SettingReproductive health center.Patient(s)180 in vitro fertilization (IVF) patients.Intervention(s)None.Main outcome measure(s)Nineteen HDL components including HDL cholesterol and free (unesterified) and esterified forms, phospholipids, triglycerides, apolipoproteins A-1 and A-2, paraoxonase 1 (PON1) activities, and seven lipophilic vitamins and micronutrients.Result(s)We collected FF specimens from two contralateral follicles on the day of oocyte retrieval and analyzed them for HDL components, characterizing the analytes by age, body mass index (BMI), race and smoking. For some analytes, a majority of total measurement variability was attributed to sources between follicles, suggesting an important role for the integrity of the blood-follicle barrier and in situ remodeling of plasma-derived constituents. For other analytes, variability was mostly attributed to sources between women, likely indicative of plasma levels. Variability between follicles decreased with increasing age and differed by BMI and smoking, and generally were lower for Asians and women with diminished ovarian reserve.Conclusion(s)Substantial variability in FF HDL components exist between follicles among women undergoing IVF as well as between women by age, BMI, race, smoking, and infertility diagnosis

Variability in the components of high-density lipoprotein particles measured in human ovarian follicular fluid: a cross-sectional analysis

ObjectiveTo assess the variability of follicular fluid (FF) high-density lipoprotein (HDL) particle components.DesignCross-sectional design with assessment using two-stage nested analysis of variance.SettingReproductive health center.Patient(s)180 in vitro fertilization (IVF) patients.Intervention(s)None.Main outcome measure(s)Nineteen HDL components including HDL cholesterol and free (unesterified) and esterified forms, phospholipids, triglycerides, apolipoproteins A-1 and A-2, paraoxonase 1 (PON1) activities, and seven lipophilic vitamins and micronutrients.Result(s)We collected FF specimens from two contralateral follicles on the day of oocyte retrieval and analyzed them for HDL components, characterizing the analytes by age, body mass index (BMI), race and smoking. For some analytes, a majority of total measurement variability was attributed to sources between follicles, suggesting an important role for the integrity of the blood-follicle barrier and in situ remodeling of plasma-derived constituents. For other analytes, variability was mostly attributed to sources between women, likely indicative of plasma levels. Variability between follicles decreased with increasing age and differed by BMI and smoking, and generally were lower for Asians and women with diminished ovarian reserve.Conclusion(s)Substantial variability in FF HDL components exist between follicles among women undergoing IVF as well as between women by age, BMI, race, smoking, and infertility diagnosis

Associations between PON1 enzyme activities in human ovarian follicular fluid and serum specimens.

The importance of high-density lipoprotein (HDL) particle components to reproduction is increasingly recognized, including the constituent paraoxonase 1 (PON1). However, the reliability characteristics of PON1 enzymes in ovarian follicular fluid (FF) as biomarkers for clinical and epidemiologic studies have not been described. Therefore, we characterized PON1 enzymes in FF and serum and assessed the impact of the PON1 Q192R polymorphism on associations between enzyme activities in two compartments. We also evaluated associations between HDL particle size and enzyme activities. We collected FF and serum from 171 women undergoing in vitro fertilization. PON1 activities were measured as paraoxonase and arylesterase activities, and HDL particle size was determined by 1H NMR spectrometry. Reliability indices for PON1 activities were characterized and we evaluated HDL particle sizes as predictors of PON1 enzyme activities. We found that PON1 enzyme activities were correlated between compartments, but higher in serum than in FF. For FF, the index of individuality (II) was low and the coefficient of variation (CV%) was high for paraoxonase activity overall (0.12 and 11.51%, respectively). However, IIs increased (0.33-1.30) and CV%s decreased (5.58%-8.52%) when stratified by PON1 Q192R phenotype. The intraclass correlation coefficient (ICC) for FF paraoxonase activity was high overall (0.89) but decreased when stratified by PON1 Q192R phenotype (0.43-0.75). We found similar, although more modest, patterns for FF arylesterase activity. For enzyme activities in serum, ICCs were close to 1.00 across all phenotypes. Additionally, different HDL particle sizes predicted PON1 enzyme activities according to PON1 Q192R phenotype. Overall, stratification by PON1 Q192R phenotype improved the reliability characteristics of FF PON1 enzymes as biomarkers for use in clinical investigations but diminished usefulness for epidemiologic studies. Thus, we recommend stratification by PON1 Q192R phenotype for clinical but not epidemiologic investigations, when employing FF PON1 enzyme activity biomarkers

Distribution of demographic and clinical factors by <i>PON1</i> Q192R phenotype among <i>in vitro</i> fertilization patients (n = 171).

<p>Distribution of demographic and clinical factors by <i>PON1</i> Q192R phenotype among <i>in vitro</i> fertilization patients (n = 171).</p

Multivariable linear regression models of follicular fluid (FF) PON1 activities associated with size-specific high-density lipoprotein (HDL) particles (μmol/L), according to <i>PON1</i> Q192R phenotype.

<p>Multivariable linear regression models of follicular fluid (FF) PON1 activities associated with size-specific high-density lipoprotein (HDL) particles (μmol/L), according to <i>PON1</i> Q192R phenotype.</p

Multivariable linear regression models of follicular fluid (FF) and serum PON1 activities associated with high-density lipoprotein (HDL) particles (μmol/L), according to <i>PON1</i> Q192R phenotype.

<p>Multivariable linear regression models of follicular fluid (FF) and serum PON1 activities associated with high-density lipoprotein (HDL) particles (μmol/L), according to <i>PON1</i> Q192R phenotype.</p

Preconception serum lipids and lipophilic micronutrient levels are associated with live birth rates after IVF

Research questionIs a mixture of preconception serum lipids and lipophilic micronutrients associated with clinical pregnancy and live births?DesignIn this prospective cohort study, blood serum was collected on the day of oocyte retrieval for 180 women undergoing IVF at an academic reproductive health centre. Concentrations of lipids (phospholipids, total cholesterol, high- and low-density lipoproteins, and triglycerides) and lipophilic micronutrients (α-, δ-, and γ-tocopherols, retinol, β- and α-carotenes, β-cryptoxanthin, lutein and lycopene) were determined using diagnostic reagent kits and high-performance liquid chromatography. Poisson regression was used with robust variance estimation to evaluate changes in Z-scores for the mixture of serum lipid and lipophilic micronutrient concentrations as predictors of embryo implantation, clinical pregnancy and live birth, adjusted for age, body mass index (BMI), race, smoking status, infertility diagnosis, ovarian stimulation protocol and other measured lipid and lipophilic micronutrient concentrations.ResultsEach SD higher serum triglyceride concentration was associated with a lower chance of live birth (RR 0.54; 95% CI 0.33 to 0.90) whereas a 1 SD higher serum α-tocopherol concentration, as part of a mixture of serum lipids and lipophilic micronutrients, was associated with a higher likelihood for a live birth (RR 1.61; 95% CI 1.11 to 2.36). Serum β-carotene concentrations were associated with live birth in a non-linear fashion; low β-carotene was associated with a lower chance of live birth and high β-carotene with a higher chance of live birth.ConclusionAlthough components of a mixture of lipids and lipophilic micronutrients were associated with live birth outcomes after IVF, a larger investigation is necessary to fully evaluate the potential clinical implications

Characteristics of biological variability for concentrations of PON activities measured in follicular fluid (FF) and serum by <i>PON1</i> Q192R phenotype among <i>in vitro</i> fertilization patients.

<p>Characteristics of biological variability for concentrations of PON activities measured in follicular fluid (FF) and serum by <i>PON1</i> Q192R phenotype among <i>in vitro</i> fertilization patients.</p