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1.  Associations between toxic metals in follicular fluid and in vitro fertilization (IVF) outcomes 
Purpose
We previously reported associations between trace concentrations of Hg, Cd and Pb in blood and urine and reproductive outcomes for women undergoing in-vitro fertilization (IVF). Here we assess measurements in single follicular fluid (FF) specimens from 46 women as a presumably more relevant marker of dose for reproductive toxicity.
Methods
FF specimens were analyzed for Hg, Cd and Pb using sector field-inductively coupled plasma-mass spectrometry (SF-ICP-MS). Variability sources were assessed by nested ANOVA. Multivariable regression was used to evaluate associations for square root transformed metals with IVF outcomes, adjusting for confounders.
Results
An inverse association is detected for FF Pb and fertilization (relative risk (RR) = 0.68, P = 0.026), although positive for Cd (RR = 9.05, P = 0.025). While no other statistically significant associations are detected, odds ratios (OR) are increased for embryo cleavage with Hg (OR = 3.83, P = 0.264) and Cd (OR = 3.18, P = 0.644), and for embryo fragmentation with Cd (OR = 4.08, P = 0.586) and Pb (OR = 2.22, P = 0.220). Positive estimates are observed for Cd with biochemical (RR = 19.02, P = 0.286) and clinical pregnancies (RR = 38.80, P = 0.212), yet with very low precision.
Conclusions
We have identified associations between trace amounts of Pb and Cd in FF from a single follicle, and oocyte fertilization. Yet, the likelihood of biological variation in trace element concentrations within and between follicles, coupled with levels that are near the limits of detection suggest that future work should examine multiple follicles using a ‘one follicle-one oocyte/embryo’ approach. A larger study is merited to assess more definitively the role that these environmental factors could play with respect to egg quality in IVF programs.
doi:10.1007/s10815-012-9882-z
PMCID: PMC3528869  PMID: 23229520
Cadmium (Cd); Follicular fluid (FF); in vitro fertilization (IVF); Lead (Pb); Mercury (Hg); Reproductive outcomes
2.  DNA methylation changes in whole blood is associated with exposure to the environmental contaminants, mercury, lead, cadmium and bisphenol A, in women undergoing ovarian stimulation for IVF 
Human Reproduction (Oxford, England)  2012;27(5):1401-1410.
BACKGROUND
Changes in DNA methylation may play an important role in the deleterious reproductive effects reported in association with exposure to environmental pollutants. In this pilot study, we identify candidate methylation changes associated with exposure to pollutants in women undergoing in vitro fertilization (IVF).
METHODS
Blood and urine were collected from women on the day of oocyte retrieval. Whole blood was analyzed for mercury and lead, and urine for cadmium using inductively coupled plasma mass spectrometry. Unconjugated bisphenol A (BPA) was analyzed in serum using high-performance liquid chromatography with Coularray detection. Participants were dichotomized as higher or lower exposure groups by median concentrations. Using the Illumina GoldenGate Methylation Cancer Panel I, DNA methylation in whole blood from 43 women was assessed at 1505 CpG sites for association with exposure levels of each pollutant. Candidate CpG sites were identified using a Diff Score >|13| (P< 0.05) and an absolute difference >10% which were confirmed using bisulfite pyrosequencing.
RESULTS
Methylation of the GSTM1/5 promoter was increased for women with higher mercury exposure (P= 0.04); however, no correlation was observed (r= 0.17, P= 0.27). Reduced methylation was detected in the COL1A2 promoter in women with higher exposure to lead (P= 0.004), and an inverse correlation was observed (r = − 0.45, P= 0.03). Lower methylation of a promoter CpG site at the TSP50 gene was detected in women with higher BPA exposure (P= 0.005), and again an inverse correlation was identified (r = − 0.51, P= 0.001).
CONCLUSIONS
Altered DNA methylation at various CpG sites was associated with exposure to mercury, lead or BPA, providing candidates to be investigated using a larger study sample, as the results may reflect an independently associated predictor (e.g. socioeconomic status, diet, genetic variants, altered blood cell composition). Further studies accommodating variations in these factors will be needed to confirm these associations and identify their underlying causes.
doi:10.1093/humrep/des038
PMCID: PMC3329190  PMID: 22381621
bisphenol A (BPA); DNA methylation; IVF; lead (Pb); mercury (Hg)
3.  Occupational Exposure to Ultraviolet Radiation and Risk of Non-Melanoma Skin Cancer in a Multinational European Study 
PLoS ONE  2013;8(4):e62359.
Background
Studies suggest that ambient sunlight plays an important role in the pathogenesis of non-melanoma skin cancers (NMSC). However, there is ongoing controversy regarding the relevance of occupational exposure to natural and artificial ultraviolet radiation (UV) radiation.
Objectives
We investigated potential associations between natural and artificial UV radiation exposure at work with NMSC in a case-control study conducted in Hungary, Romania, and Slovakia.
Methods
Occupational exposures were classified by expert assessment for 527 controls and 618 NMSC cases (515 basal cell carcinoma, BCC). Covariate information was collected via interview and multiple logistic regression models were used to assess associations between UV exposure and NMSC.
Results
Lifetime prevalence of occupational exposure in the participants was 13% for natural UV radiation and 7% for artificial UV radiation. Significant negative associations between occupational exposure to natural UV radiation and NMSC were detected for all who had ever been exposed (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.27–0.80); similar results were detected using a semi-quantitative metric of cumulative exposure. The effects were modified by skin complexion, with significantly decreased risks of BCC among participants with light skin complexion. No associations were observed in relation to occupational artificial UV radiation exposure.
Conclusions
The protective effect of occupational exposure to natural UV radiation was unexpected, but limited to light-skinned people, suggesting adequate sun-protection behaviors. Further investigations focusing on variations in the individual genetic susceptibility and potential interactions with environmental and other relevant factors are planned.
doi:10.1371/journal.pone.0062359
PMCID: PMC3634731  PMID: 23638051
4.  Relation of Blood Cadmium, Lead, and Mercury Levels to Biomarkers of Lipid Peroxidation in Premenopausal Women 
American Journal of Epidemiology  2012;175(7):645-652.
Exposures to cadmium, lead, and mercury are associated with adverse health effects, including cardiovascular disease, which may be promoted by lipid peroxidation. The authors examined cadmium, lead, and mercury in relation to plasma levels of F2-8α isoprostanes (isoprostane), 9-hydroperoxy-10,12-octadecadienoic acid (9-HODE), 13-hydroxy-9,11-octadecadienoic acid (13-HODE), and thiobarbituric acid reactive substances (TBARS) in 252 women from western New York State (2005–2007). Healthy premenopausal women were followed for ≤2 menstrual cycles, with biomarkers of lipid peroxidation being assessed ≤8 times per cycle. Metals were measured at baseline in whole blood. Linear mixed models were used to estimate the association between cadmium, lead, and mercury and lipid peroxidation biomarkers. Median cadmium, lead, and mercury levels were 0.30 μg/L, 0.86 μg/dL, and 1.10 μg/L, respectively. Blood cadmium, lead, and mercury were not associated with increases in isoprostane, TBARS, 9-HODE, or 13-HODE levels. Isoprostane levels decreased 6.80% (95% confidence interval: −10.40, −3.20) per 1% increase in mercury. However, after adjustment for a simulated strong confounding factor, such as precisely measured fish consumption, the observed association was attenuated, suggesting that this unexpected association could be attributable to unmeasured confounding. In this population of healthy premenopausal women with low exposure levels, cadmium, lead, and mercury were not associated with elevated lipid peroxidation biomarkers.
doi:10.1093/aje/kwr375
PMCID: PMC3324434  PMID: 22302120
cadmium; hydroxyl-octadecadienoic acid; isoprostane; lead; mercury; oxidative stress; thiobarbituric acid reactive substances; women
5.  Serum unconjugated bisphenol A concentrations in men may influence embryo quality indicators during in vitro fertilization 
Here we assess bisphenol A (BPA) in couples undergoing in vitro fertilization (IVF) and indicators of embryo quality; embryo cell number (ECN) and embryo fragmentation score (EFS). Twenty-seven couples provided serum on the day of oocyte retrieval. Unconjugated BPA was measured by HPLC with Coularray detection. Odds ratios (OR) were generated using ordinal logistic regression including female and male BPA concentrations, age and race, and day of embryo transfer for ECN. Inverse associations are suggested for male BPA with ECN (OR=0.70, P=0.069), and EFS (OR=0.54, P=0.009), but not for women. Male BPA exposure may affect embryo quality during IVF.
doi:10.1016/j.etap.2011.06.003
PMCID: PMC3157013  PMID: 21843814
Assisted reproduction; Bisphenol A (BPA); Embryo; in vitro Fertilization (IVF); Infertility
6.  Bisphenol A exposure reduces the estradiol response to gonadotropin stimulation during in vitro fertilization 
Fertility and sterility  2011;96(3):672-677.e2.
Objective
Investigate associations between serum BPA concentrations and follicular response to exogenous ovary stimulation.
Design
Fasting serum was prospectively collected on the day of oocyte retrieval and assessed for unconjugated BPA using high-performance liquid chromatography (HPLC) with Coularray detection. Multivariable linear regression and negative binomial regression were used to assess associations between concentrations of BPA and outcome measures. Models were adjusted for race/ethnicity, antral follicle count at baseline, and cigarette smoking.
Setting
A reproductive health center.
Patients
Forty-four women undergoing in vitro fertilization (IVF).
Main outcome measures
Peak-estradiol level (E2) and the number of oocytes retrieved during IVF.
Results
The median unconjugated serum BPA concentration is 2.53 ng/ml (range 0.3–67.36 ng/ml). Bisphenol A is inversely associated with E2 (β=−0.16; 95% confidence interval (CI) −0.32, 0.01), as well as with E2 normalized to the number of mature-sized follicles at the hCG trigger (β=−0.14; 95%CI −0.24, −0.03). No association is observed for BPA and the number of oocytes retrieved (adjusted risk ratio=0.95; 95%CI 0.82, 1.10).
Conclusions
Bisphenol A is associated with a reduced estradiol response during IVF. Although limited by the preliminary nature of this study, these results merit confirmation in a future comprehensive investigation.
doi:10.1016/j.fertnstert.2011.06.063
PMCID: PMC3168558  PMID: 21813122
Bisphenol A (BPA); Estradiol (E2); Follicle; In vitro fertilization (IVF); Ovary
7.  Thyroid Function and Perfluoroalkyl Acids in Children Living Near a Chemical Plant 
Environmental Health Perspectives  2012;120(7):1036-1041.
Background: Animal studies suggest that some perfluoroalkyl acids (PFAAs), including perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononanoic acid (PFNA) may impair thyroid function. Epidemiological findings, mostly related to adults, are inconsistent.
Objectives: We investigated whether concentrations of PFAAs were associated with thyroid function among 10,725 children (1–17 years of age) living near a Teflon manufacturing facility in the Mid-Ohio Valley (USA).
Methods: Serum levels of thyroid-stimulating hormone (TSH), total thyroxine (TT4), and PFAAs were measured during 2005–2006, and information on diagnosed thyroid disease was collected by questionnaire. Modeled in utero PFOA concentrations were based on historical information on PFOA releases, environmental distribution, pharmacokinetic modeling, and residential histories. We performed multivariate regression analyses.
Results: Median concentrations of modeled in utero PFOA and measured serum PFOA, PFOS, and PFNA were 12, 29, 20, and 1.5 ng/mL, respectively. The odds ratio for hypothyroidism (n = 39) was 1.54 [95% confidence interval (CI): 1.00, 2.37] for an interquartile range (IQR) contrast of 13 to 68 ng/mL in serum PFOA measured in 2005–2006. However, an IQR shift in serum PFOA was not associated with TSH or TT4 levels in all children combined. IQR shifts in serum PFOS (15 to 28 ng/mL) and serum PFNA (1.2 to 2.0 ng/mL) were both associated with a 1.1% increase in TT4 in children 1–17 years old (95% CIs: 0.6, 1.5 and 0.7, 1.5 respectively).
Conclusions: This is the first large-scale report in children suggesting associations of serum PFOS and PFNA with thyroid hormone levels and of serum PFOA and hypothyroidism.
doi:10.1289/ehp.1104370
PMCID: PMC3404658  PMID: 22453676
children; PFAA; PFNA; PFOA; PFOS; T4; thyroid disease; thyroid hormones; TSH
8.  Cholesterol, endocrine and metabolic disturbances in sporadic anovulatory women with regular menstruation 
BACKGROUND
Sporadic anovulation among regularly menstruating women is not well understood. It is hypothesized that cholesterol abnormalities may lead to hormone imbalances and incident anovulation. The objective was to evaluate the association between lipoprotein cholesterol levels and endocrine and metabolic disturbances and incident anovulation among ovulatory and anovulatory women reporting regular menstruation.
METHODS
The BioCycle Study was a prospective cohort study conducted at the University at Buffalo from September 2005 to 2007, which followed 259 self-reported regularly menstruating women aged 18–44 years, for one or two complete menstrual cycles. Sporadic anovulation was assessed across two menstrual cycles.
RESULTS
Mean total and low-density lipoprotein cholesterol and triglycerides levels across the menstrual cycles were higher during anovulatory cycles (mean difference: 4.6 (P = 0.01), 3.0 (P = 0.06) and 6.4 (P = 0.0002) mg/dl, respectively, adjusted for age and BMI). When multiple total cholesterol (TC) measures prior to expected ovulation were considered, we observed a slight increased risk of anovulation associated with increased levels of TC (odds ratio per 5 mg/dl increase, 1.07; 95% confidence interval, 0.99, 1.16). Sporadic anovulation was associated with an increased LH:FSH ratio (P = 0.002), current acne (P = 0.02) and decreased sex hormone-binding globulin levels (P = 0.005).
CONCLUSIONS
These results do not support a strong association between lipoprotein cholesterol levels and sporadic anovulation. However, sporadic anovulation among regularly menstruating women is associated with endocrine disturbances which are typically observed in women with polycystic ovary syndrome.
doi:10.1093/humrep/deq322
PMCID: PMC3024896  PMID: 21115506
anovulation; lipoproteins; menstrual cycle; endocrine disturbances
9.  Associations between blood metals and fecundity among women residing in New York State 
Trace exposures to metals may affect female reproductive health. To assess the relation between trace concentrations of blood metals and female fecundity, 99 non-pregnant women discontinuing contraception for the purpose of becoming pregnant were prospectively followed. Participants completed a baseline interview and daily diaries until pregnant, or up to 12 menstrual cycles at risk for pregnancy; home pregnancy test kits were used. For 80 women, whole blood specimens were analyzed for arsenic, cadmium, lead, magnesium, nickel, selenium and zinc using inductively coupled plasma mass spectrometry (ICP-MS). Time to pregnancy was estimated using Cox proportional hazards models for discrete time. Metal concentrations were generally within population reference intervals. Adjusted models suggest a 51.5% increase in the probability for pregnancy per 3.60 μg/L increase in Mg (P=0.062), and a 27.7% decrease per 0.54 μg/L increase in Zn (P=0.114). Findings indicate that Mg and Zn may impact female fecundity, but in varying directions.
doi:10.1016/j.reprotox.2010.09.013
PMCID: PMC3039711  PMID: 20933593
Arsenic (As); Cadmium (Cd); fecundity; Lead (Pb); Magnesium (Mg); Nickel (Ni); Selenium (Se); Zinc (Zn)
10.  Toxic trace metals and human oocytes during in vitro fertilization (IVF) 
Trace exposures to the toxic metals mercury (Hg), cadmium (Cd) and lead (Pb) may threaten human reproductive health. The aim of this study is to generate biologically-plausible hypotheses concerning associations between Hg, Cd, and Pb and in vitro fertilization (IVF) endpoints. For 15 female IVF patients, a multivariable log-binomial model suggests a 75% reduction in the probability for a retrieved oocyte to be in metaphase-II arrest for each μg/dL increase in blood Pb concentration (relative risk (RR) = 0.25, 95% confidence interval (CI) 0.03–2.50, P = 0.240). For 15 male IVF partners, each μg/L increase in urine Cd concentration is associated with an 81% decrease in the probability for oocyte fertilization (RR = 0.19, 95% CI 0.03–1.35, P = 0.097). Because of the magnitude of the effects, these results warrant a comprehensive study with sufficient statistical power to further evaluate these hypotheses.
doi:10.1016/j.reprotox.2010.01.003
PMCID: PMC2882801  PMID: 20096775
Mercury (Hg); cadmium (Cd); lead (Pb); oocyte maturation; oocyte fertilization; in vitro fertilization (IVF); assisted reproductive technologies (ART); intracytoplasmic sperm injection (ICSI)
11.  Finger bone immaturity and 2D:4D ratio measurement error in the assessment of the hyperandrogenic hypothesis for the etiology of autism spectrum disorders 
Physiology & behavior  2010;100(3):221-224.
Emerging hypotheses suggest a causal role for prenatal androgen exposure in some cases of autism spectrum disorders (ASD). The ratios of the lengths of the bones of the 2nd to the 4th digit (2D:4D) are purported to be markers for prenatal androgen exposure and to be established early in gestation. Elongation of the 4th digit in response to testosterone is said to reduce 2D:4D in males versus females. We examined the ratios of bones from the left hand radiographs of 75 boys and 6 girls 4–8 years of age, diagnosed with ASD, to evaluate digit ratio as a marker for gestational androgen exposure. Contrary to our expectations, girls had reduced 2D:4D compared to boys but the difference was not significant (Cohen’s D 0.51–0.66, P>0.05). The limited sample size for this study and the absence of a referent group precluded providing robust estimates for girls and identifying possible statistical differences between the sexes. Tanner-Whitehouse 3 (TW3) rating of finger bone growth suggested relative immaturity of the 4th relative to the 2nd digits. Positive correlations were detected for 2D:4D ratios, body mass index (r=0.23, P=0.039), chronologic age (r=0.35, P=0.001), and skeletal age (r=0.42, P<0.0001). The TW3 ratings and associations between 2D:4D ratios and indicators of growth suggest that digits develop at different rates. This asynchronous development may produce differences in 2D:4D over time which could lead to erroneous interpretation of androgen exposure in utero among young ASD children.
doi:10.1016/j.physbeh.2010.01.005
PMCID: PMC2897171  PMID: 20093135
Autism spectrum disorder; digit ratio; hyperandrogenic hypothesis; measurement error
12.  Recent cadmium exposure among male partners may affect oocyte fertilization during in vitro fertilization (IVF) 
Purpose
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.
Methods
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.
Results
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).
Conclusions
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.
doi:10.1007/s10815-010-9437-0
PMCID: PMC2941586  PMID: 20508982
Cadmium (Cd); Oocyte fertilization; In vitro fertilization (IVF); Assisted reproductive technologies (ART)
13.  Changes in Maternal Serum Chlorinated Pesticide Concentrations across Critical Windows of Human Reproduction and Development 
Environmental research  2008;109(1):93-100.
Investigators often employ a single cross-sectional measure of in utero exposure when evaluating associations between organochlorine pesticides/ metabolites (OCs) and adverse reproductive outcomes. Few data are available on the stability of exposures to OCs over critical windows of human reproduction and development inclusive of the periconception window. Our objective was to measures changes in OC concentrations prior to conception and throughout pregnancy or after 12 unsuccessful months attempting pregnancy. Seventy-nine women planning pregnancy were prospectively enrolled and followed for up to 12 menstrual cycles. Blood specimens were obtained for toxicologic analysis of seven OCs from participating women at baseline (preconception, n=79), at the first prenatal visit following a positive pregnancy test leading to a live birth (n=54) or after pregnancy loss (n=10), at approximately 6 weeks post-partum (n=53), and after 12 unsuccessful cycles (n=9). Overall and daily rate of change in OCs concentration (ng/g serum) were estimated adjusting for serum lipids and baseline concentration. Significant (P<0.05) decreases in the overall and daily rate of change in OCs concentrations (ng/mL serum) were observed from baseline to pregnancy for HCB (−0.032, −0.001, respectively) and trans-nonachlor (−0.050, −0.002, respectively) while oxychlordane demonstrated an increase during this critical window (0.029, 0.001, respectively). Significant decreases in aldrin (−0.002, −1.47 × 10−4, respectively), HCB (−0.069, −0.003, respectively), and trans-nonachlor (−0.045, −0.002 respectively), and an overall increase for oxychlordane (0.015) were seen for women with pregnancy losses. Significant decreases also were observed among infertile women for aldrin (−0.003, −3.52 × 10−6, respectively), DDE (−0.210, −4.29 × 10−4, respectively), and HCB (−0.096, −2.03 × 10−4, respectively), along with an increase for trans-nonachlor (0.034, 7.59 × 10−5, respectively). These data, though limited by sample size and the possibility of laboratory measurement error, suggest that OC concentrations may change over critical windows. This underscores the importance of timing biospecimen collection to critical windows for development in the assessment of reproductive and/or developmental effects.
doi:10.1016/j.envres.2008.08.013
PMCID: PMC2606911  PMID: 18973878
critical windows; organochlorine pesticides; persistent organic pollutants; pregnancy; pregnancy loss
14.  Follicular fluid high density lipoprotein-associated micronutrient levels are associated with embryo fragmentation during IVF 
Purpose
To investigate whether follicular fluid lipid-soluble micronutrients are associated with embryo morphology parameters during IVF.
Methods
Follicle fluid and oocytes were obtained prospectively from 81 women. Embryo morphology parameters were used as surrogate markers of oocyte health. HDL lipids and lipid-soluble micronutrients were analyzed by high-pressure liquid chromatography. Non-parametric bi-variate analysis and multivariable ordinal logistic regression models were employed to examine associations between biochemical and embryo morphology parameters.
Results
Follicular fluid HDL cholesterol (r = −0.47, p < 0.01), α-tocopherol (r = −0.41, p < 0.01), δ-tocopherol (r = −0.38, p < 0.05) and β-cryptoxanthine (r = −0.42, p < 0.01) are negatively correlated with embryo fragmentation. Ordinal logistic regression models indicate that a 0.1 μmol/L increase in β-cryptoxanthine, adjusted for γ-tocopherol, is associated with a 75% decrease in the cumulative odds of higher embryo fragmentation (p = 0.010).
Conclusion
Follicular fluid HDL micronutrients may play an important role in the development of the human oocyte as evident by embryo fragmentation during IVF.
doi:10.1007/s10815-009-9367-x
PMCID: PMC2799562  PMID: 19921421
High density lipoprotein; Tocopherols; Carotenoids; Embryo fragmentation; In vitro fertilization
16.  Analytical and biological variation of biomarkers of oxidative stress during the menstrual cycle 
Little information is available on the intra-individual variability of oxidative stress biomarkers in healthy individuals and even less in the context of the menstrual cycle. The objective of this study was to characterize the analytical and biological variability of a panel of 21 markers of oxidative damage, antioxidant defence and micronutrients in nine healthy, regularly menstruating women aged 18–44 years. Analyses included measurement of lipid peroxidation, antioxidant enzymes and antioxidant vitamins. Blood specimens were collected, processed and stored using standardized procedures on days 2, 7, 12, 13, 14, 18, 22 and 28 in one cycle for each subject. Replicate analyses of markers were performed and two-way nested random effects ANOVA was used to describe analytical, intra-individual and inter-individual variability. No statistically significant differences at α = 0.05, or temporal effects across the menstrual cycle were observed. Analytical variability was the smallest component of variance for all variables. The ICC among replicates ranged from 0.80 to 0.98. Imprecision based on quality control materials ranged from 1 to 11%. The critical differences between serial results varied greatly between assays ranging from 6 to 216% of the mean level. These results provide important initial information on the variability of biomarkers of oxidative stress, antioxidant defence and micronutrients across the menstrual cycle.
doi:10.1080/13547500701775563
PMCID: PMC2504010  PMID: 18270869
Oxidative stress; antioxidants; biological variation; menstrual cycle
17.  The use and misuse of matching in case-control studies: the example of PCOS 
Fertility and sterility  2007;88(3):707-710.
Matching control selection strategies are often employed in PCOS case-control studies; however, they are infrequently used in an appropriate fashion. When properly applied, matching may offer improved study precision, but this is highly contingent on the causal pathway under consideration, strength of the associations between the matching variable and both the risk factor of interest and PCOS, and use of an appropriate stratified data analysis.
doi:10.1016/j.fertnstert.2006.11.125
PMCID: PMC2040105  PMID: 17433314
18.  Maternal Serum Polychlorinated Biphenyl Concentrations across Critical Windows of Human Development 
Environmental Health Perspectives  2007;115(9):1320-1324.
Background
Few data are available on polychlorinated biphenyl (PCB) concentrations over critical windows of human reproduction and development inclusive of the periconception window.
Objectives
Our goal was to measure changes in PCB concentrations from preconception to pregnancy, through pregnancy, or after a year without becoming pregnant.
Methods
Seventy-nine women planning pregnancies were prospectively enrolled and followed for up to 12 menstrual cycles of attempting pregnancy. Blood specimens were obtained from participating women preconceptionally (n = 79), after a positive pregnancy test leading to a live birth (n = 54) or pregnancy loss (n = 10), at approximately 6 weeks postpartum (n = 53), and after 12 unsuccessful cycles (n = 9) for toxicologic analysis of 76 PCB congeners. We estimated overall and daily rate of change in PCB concentration (nanograms per gram serum) adjusting for relevant covariates, serum lipids, and baseline PCB concentration.
Results
Significant (p < 0.0001) decreases in the mean overall and daily rate of change in PCB concentrations were observed between the preconception and first pregnancy samples for total (–1.012 and –0.034, respectively), estrogenic (–0.444 and –0.016, respectively), and antiestrogenic (–0.106 and –0.004, respectively) PCBs among women with live births. Similar significant decreases in total (–1.452 and –0.085), estrogenic (–0.647 and –0.040), and antiestrogenic (–0.093 and –0.004) PCB concentrations were seen for women with pregnancy losses. No significant changes were observed for PCB congener 153.
Conclusions
These data suggest that PCB concentrations may change during the periconception interval, questioning the stability of persistent compounds during this critical window.
doi:10.1289/ehp.10086
PMCID: PMC1964915  PMID: 17805422
critical windows; infertility; periconception; persistent organic pollutants; polychlorinated biphenyls (PCBs); pregnancy loss

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