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The number of in vitro fertilization (IVF) cycles in the United States increased from fewer than 46,000 in 1995 to more than 120,000 in 2005. IVF and other assisted reproductive technology (ART) data are routinely collected and used to identify outcome predictors. However, researchers do not always make full use of the data due to their complexity. Design approaches have included restriction to first-cycle attempts only, which reduces power and identifies effects only of those factors associated with initial success. Many statistical techniques have been used or proposed for analysis of IVF data, ranging from simple t tests to sophisticated models designed specifically for IVF. We applied several of these methods to data from a prospective cohort of 2687 couples undergoing ART from 1994 through 2003. Results across methods are compared and the appropriateness of the various methods is discussed with the intent to illustrate methodologic validity. We observed a remarkable similarity of coefficient estimates across models. However, each method for dealing with multiple cycle data relies on assumptions that may or may not be expected to hold in a given IVF study. The robustness and reported magnitude of effect for individual predictors of IVF success may be inflated or attenuated due to violation of statistical assumptions, and should always be critically interpreted. Given that risk factors associated with IVF success may also advance our understanding of the physiologic processes underlying conception, implantation, and gestation, the application of valid methods to these complex data is critical. © 2011 by Lippincott Williams & Wilkins.

The number of in vitro fertilization (IVF) cycles in the United States increased from fewer than 46,000 in 1995 to more than 120,000 in 2005. IVF and other assisted reproductive technology (ART) data are routinely collected and used to identify outcome predictors. However, researchers do not always make full use of the data due to their complexity. Design approaches have included restriction to first-cycle attempts only, which reduces power and identifies effects only of those factors associated with initial success. Many statistical techniques have been used or proposed for analysis of IVF data, ranging from simple t tests to sophisticated models designed specifically for IVF. We applied several of these methods to data from a prospective cohort of 2687 couples undergoing ART from 1994 through 2003. Results across methods are compared and the appropriateness of the various methods is discussed with the intent to illustrate methodologic validity. We observed a remarkable similarity of coefficient estimates across models. However, each method for dealing with multiple cycle data relies on assumptions that may or may not be expected to hold in a given IVF study. The robustness and reported magnitude of effect for individual predictors of IVF success may be inflated or attenuated due to violation of statistical assumptions, and should always be critically interpreted. Given that risk factors associated with IVF success may also advance our understanding of the physiologic processes underlying conception, implantation, and gestation, the application of valid methods to these complex data is critical. © 2011 by Lippincott Williams & Wilkins.

BACKGROUND: Exposure to persistent organic pollutants, including polychlorinated biphenyls (PCBs) and organochlorine pesticides, is widespread among the general population. There is evidence of adverse effects on reproduction and early pregnancy in relation to organochlorine exposure but human studies remain limited. The increased use of assisted reproductive technologies (ART) presents unique opportunities for the assessment of environmental influences on early pregnancy outcomes not otherwise observable in humans, but studies need to be designed to maximize the efficiency of the exposure data collected while minimizing exposure measurement error. METHODS: The present study was conducted to assess the correlation between concentrations of organochlorines in serum and follicular fluid samples collected from a subset of women undergoing ART in a large study that took place between 1994 and 2003, as well as the temporal reliability of serum organochlorine concentrations among women undergoing multiple ART cycles in the study. PCB congeners (118, 138, 153, and 180), 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT), the DDT metabolite p,p'-DDE, hexachlorobenzene (HCB), oxychlordane, trans-nonachlor and mirex were measured in 72 follicular fluid samples and 265 serum samples collected from 110 women. RESULTS: Organochlorine concentrations in paired serum and follicular fluid samples were correlated, with Pearson and Spearman coefficients ranging from 0.60 to 0.92. Serum organochlorine concentrations were two- to three-fold greater than in follicular fluid, and a significant inverse trend was observed in the distribution of follicular fluid:serum ratios with increasing molecular weight of the compound (p-value for trend < 0.0001). Serum organochlorine concentrations were highly reliable over the course of several months, with intraclass correlation coefficients ranging from 0.86 to 0.98. Finally, there was evidence for a declining trend in organochlorine concentra

BACKGROUND: Exposure to persistent organic pollutants, including polychlorinated biphenyls (PCBs) and organochlorine pesticides, is widespread among the general population. There is evidence of adverse effects on reproduction and early pregnancy in relation to organochlorine exposure but human studies remain limited. The increased use of assisted reproductive technologies (ART) presents unique opportunities for the assessment of environmental influences on early pregnancy outcomes not otherwise observable in humans, but studies need to be designed to maximize the efficiency of the exposure data collected while minimizing exposure measurement error. METHODS: The present study was conducted to assess the correlation between concentrations of organochlorines in serum and follicular fluid samples collected from a subset of women undergoing ART in a large study that took place between 1994 and 2003, as well as the temporal reliability of serum organochlorine concentrations among women undergoing multiple ART cycles in the study. PCB congeners (118, 138, 153, and 180), 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT), the DDT metabolite p,p'-DDE, hexachlorobenzene (HCB), oxychlordane, trans-nonachlor and mirex were measured in 72 follicular fluid samples and 265 serum samples collected from 110 women. RESULTS: Organochlorine concentrations in paired serum and follicular fluid samples were correlated, with Pearson and Spearman coefficients ranging from 0.60 to 0.92. Serum organochlorine concentrations were two- to three-fold greater than in follicular fluid, and a significant inverse trend was observed in the distribution of follicular fluid:serum ratios with increasing molecular weight of the compound (p-value for trend < 0.0001). Serum organochlorine concentrations were highly reliable over the course of several months, with intraclass correlation coefficients ranging from 0.86 to 0.98. Finally, there was evidence for a declining trend in organochlorine concentra

Widespread application of contemporary-use insecticides results in low-level exposure for a majority of the population through a variety of pathways. Urinary insecticide biomarkers account for all exposure pathways, but failure to account for temporal within-subject variability of urinary levels can lead to exposure misclassification. To examine temporal variability in urinary markers of contemporary-use insecticides, nine repeated urine samples were collected over 3 months from 10 men participating in an ongoing study of male reproductive health. These 90 samples were analyzed for urinary metabolites of chlorpyrifos (3,5,6-trichloro-2-pyridinol (TCPY)) and carbaryl (1-naphthol (1N)). Volume- based (unadjusted), as well as creatinine (CRE)- and specific gravity (SG)-adjusted concentrations were measured. TCPY had low reliability with an intraclass correlation coefficient between 0.15 and 0.21, while IN was moderately reliable with an intraclass correlation coefficient between 0.55 and 0.61. When the 10 men were divided into tertiles based on 3-month geometric mean TCPY and 1N levels, a single urine sample performed adequately in classifying a subject into the highest or lowest exposure tertiles. Sensitivity and specificity ranged from 0.44 to 0.84 for TCPY and from 0.56 to 0.89 for IN. Some differences in the results between unadjusted metabolite concentrations and concentrations adjusted for CRE and SG were observed. Questionnaires were used to assess diet in the 24 h preceding the collection of each urine sample. In mixed-effects models, TCPY was significantly associated with season as well as with consuming grapes and cheese, while IN levels were associated with consuming strawberries. In conclusion, although a single sample adequately predicted longer-term average exposure, a second sample collected at least 1 month following the first sample would reduce exposure measurement error. © 2005 Nature Publishing Group All rights reserved.

Widespread application of contemporary-use insecticides results in low-level exposure for a majority of the population through a variety of pathways. Urinary insecticide biomarkers account for all exposure pathways, but failure to account for temporal within-subject variability of urinary levels can lead to exposure misclassification. To examine temporal variability in urinary markers of contemporary-use insecticides, nine repeated urine samples were collected over 3 months from 10 men participating in an ongoing study of male reproductive health. These 90 samples were analyzed for urinary metabolites of chlorpyrifos (3,5,6-trichloro-2-pyridinol (TCPY)) and carbaryl (1-naphthol (1N)). Volume- based (unadjusted), as well as creatinine (CRE)- and specific gravity (SG)-adjusted concentrations were measured. TCPY had low reliability with an intraclass correlation coefficient between 0.15 and 0.21, while IN was moderately reliable with an intraclass correlation coefficient between 0.55 and 0.61. When the 10 men were divided into tertiles based on 3-month geometric mean TCPY and 1N levels, a single urine sample performed adequately in classifying a subject into the highest or lowest exposure tertiles. Sensitivity and specificity ranged from 0.44 to 0.84 for TCPY and from 0.56 to 0.89 for IN. Some differences in the results between unadjusted metabolite concentrations and concentrations adjusted for CRE and SG were observed. Questionnaires were used to assess diet in the 24 h preceding the collection of each urine sample. In mixed-effects models, TCPY was significantly associated with season as well as with consuming grapes and cheese, while IN levels were associated with consuming strawberries. In conclusion, although a single sample adequately predicted longer-term average exposure, a second sample collected at least 1 month following the first sample would reduce exposure measurement error. © 2005 Nature Publishing Group All rights reserved.

Background: Members of the general population are exposed to non-persistent insecticides at low levels. The present study explored whether environmental exposures to carbaryl and chlorpyrifos are associated with DNA damage in human sperm. Methods: Subjects (n = 260) were recruited through a Massachusetts infertility clinic. Individual exposures were measured as spot urinary metabolite concentrations of chlorpyrifos [3,5,6-trichloro-2-pyridinol (TCPY)] and carbaryl [1-naphthol (1N)], adjusted using specific gravity. Sperm DNA integrity was assessed by neutral comet assay and reported as comet extent, percentage DNA in comet tail (Tail%) and tail distributed moment (TDM). Results: A statistically significant increase in Tail% was found for an interquartile range (IQR) increase in both 1N [coefficient = 4.1; 95% confidence interval (CI) 1.9-6.3] and TCPY (2.8; 0.9-4.6), while a decrease in TDM was associated with IQR changes in 1N (-2.2; -4.9 to 0.5) and TCPY (-2.5; -4.7 to -0.2). A negative correlation between Tail% and TDM was present only when stratified by comet extent, suggesting that Tail% and TDM may measure different types of DNA damage within comet extent strata. Conclusions: Environmental exposure to carbaryl and chlorpyrifos may be associated with increased DNA damage in human sperm, as indicated by a change in comet assay parameters. © European Society of Human Reproduction and Embryology 2004; all rights reserved.

Background: Members of the general population are exposed to non-persistent insecticides at low levels. The present study explored whether environmental exposures to carbaryl and chlorpyrifos are associated with DNA damage in human sperm. Methods: Subjects (n = 260) were recruited through a Massachusetts infertility clinic. Individual exposures were measured as spot urinary metabolite concentrations of chlorpyrifos [3,5,6-trichloro-2-pyridinol (TCPY)] and carbaryl [1-naphthol (1N)], adjusted using specific gravity. Sperm DNA integrity was assessed by neutral comet assay and reported as comet extent, percentage DNA in comet tail (Tail%) and tail distributed moment (TDM). Results: A statistically significant increase in Tail% was found for an interquartile range (IQR) increase in both 1N [coefficient = 4.1; 95% confidence interval (CI) 1.9-6.3] and TCPY (2.8; 0.9-4.6), while a decrease in TDM was associated with IQR changes in 1N (-2.2; -4.9 to 0.5) and TCPY (-2.5; -4.7 to -0.2). A negative correlation between Tail% and TDM was present only when stratified by comet extent, suggesting that Tail% and TDM may measure different types of DNA damage within comet extent strata. Conclusions: Environmental exposure to carbaryl and chlorpyrifos may be associated with increased DNA damage in human sperm, as indicated by a change in comet assay parameters. © European Society of Human Reproduction and Embryology 2004; all rights reserved.