Person:

Ford, Jennifer

Background: Cigarette smoking has been associated with worse infertility treatment outcomes, yet some studies have found null or inconsistent results. Methods: We followed 225 couples who underwent 354 fresh non-donor assisted reproductive technology (ART) cycles between 2006 and 2014. Smoking history was self-reported at study entry. We evaluated the associations between smoking patterns and ART success using multivariable discrete time Cox proportional hazards models with six time periods: cycle initiation to egg retrieval, retrieval to fertilization, fertilization to embryo transfer (ET), ET to implantation, implantation to clinical pregnancy, and clinical pregnancy to live birth to estimate hazard ratios (HR) and 95% CIs. Time-dependent interactions between smoking intensity and ART time period were used to identify vulnerable periods. Results: Overall, 26% of women and 32% of men reported ever smoking. The HR of failing in the ART cycle without attaining live birth for male and female ever smokers was elevated, but non-significant, compared to never smokers regardless of intensity (HR = 1.02 and 1.30, respectively). Female ever smokers were more likely to fail prior to oocyte retrieval (HR: 3.37; 95% CI: 1.00, 12.73). Every one cigarette/day increase in smoking intensity for females was associated with a HR of 1.02 of failing ART (95% CI: 0.97, 1.08), regardless of duration or current smoking status. Women with higher smoking intensities were most likely to fail a cycle prior to oocyte retrieval (HR: 1.07; 95% CI: 1.00, 1.16). Among past smokers, every additional year since a man had quit smoking reduced the risk of failing ART by 4% (HR: 0.96; 95% CI: 0.91, 1.00) particularly between clinical pregnancy and live birth (HR: 0.86; 95% CI: 0.76, 0.96). Conclusions: Female smoking intensity, regardless of current smoking status, is positively associated with the risk of failing ART cycles between initiation and oocyte retrieval. In men who ever smoked, smoking cessation may reduce the probability of failing ART, particularly between clinical pregnancy and live birth. Trial registration NCT00011713. Registered: 27 February 2001.

Background: Evidence from animal studies suggests that exposure to organophosphate flame retardants (PFRs) can disrupt endocrine function and impair embryo development. However, no epidemiologic studies have been conducted to evaluate effects on fertility and pregnancy outcomes. Objectives: We evaluated associations between urinary concentrations of PFR metabolites and outcomes of in vitro fertilization (IVF) treatment among couples recruited from an academic fertility clinic. Methods: This analysis included 211 women enrolled in the Environment And Reproductive Health (EARTH) prospective cohort study (2005–2015) who provided one or two urine samples per IVF cycle. We measured five urinary PFR metabolites [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert-butylphenyl phenyl phosphate (tb-PPP), and bis(1-chloro-2-propyl) phosphate (BCIPP)] using negative electrospray ionization liquid chromatography tandem mass spectrometry (LC-MS/MS). Molar concentrations of the urinary PFR metabolites were summed. We used multivariable generalized linear mixed models to evaluate the association of the PFR metabolites with IVF outcomes, accounting for multiple IVF cycles per woman. Results: Detection frequencies were high for BDCIPP (87%), DPHP (94%), and ip-PPP (80%), but low for tb-PPP (14%) and BCIPP (0%). We observed decreased success for several IVF outcomes across increasing quartiles of both summed and individual PFR metabolites (DPHP and ip-PPP) in our adjusted multivariable models. Significant declines in adjusted means from the lowest to highest quartile of ΣPFR were observed for the proportion of cycles resulting in successful fertilization (10% decrease), implantation (31%), clinical pregnancy (41%), and live birth (38%). Conclusions: Using IVF to investigate human reproduction and pregnancy outcomes, we found that concentrations of some urinary PFR metabolites were negatively associated with proportions of successful fertilization, implantation, clinical pregnancy, and live birth. https://doi.org/10.1289/EHP1021

Background: Subfertile women are at increased risk of glucose intolerance in pregnancy. Based on epidemiologic studies, exposure to certain phthalates is associated with diabetes, elevated glucose, and increased insulin resistance. Objectives: To evaluate the association between urinary phthalate metabolites and pregnancy glucose levels in women seeking medically assisted reproduction. Methods: We evaluated 245 women participating in a prospective cohort study based at a large fertility clinic who delivered live births and had data on pregnancy urinary phthalate metabolite concentrations and blood glucose levels. Urinary phthalate metabolite concentrations were from single spot urine samples collected in 1st and 2nd trimesters. Blood glucose data was abstracted from medical records for non-fasting 50-g glucose challenge tests at 24–28 weeks gestation. Multivariable linear regression models were used to evaluate associations between 7 urinary phthalate metabolites in quartiles and mean glucose adjusted for potential confounders. Results: Eighteen percent of women had glucose levels ≥ 140 mg/dL. Second trimester monoethyl phthalate (MEP) concentrations were positively associated with glucose levels, with adjusted mean (95%CI) glucose levels of 121 mg/dl (114, 128) vs. 109 mg/dL (103, 116) for women in highest and lowest quartiles, respectively. Women in the highest quartile of second trimester mono-isobutyl phthalate (MiBP) concentrations had a mean glucose level 14 mg/dL lower compared to women in the lowest quartile. No other urinary phthalate metabolites were associated with glucose levels. Conclusions: MEP and MiBP—metabolites of diethyl phthalate and dibutyl phthalate, respectively—were associated with higher pregnancy glucose in subfertile women—a population at high risk of glucose intolerance in pregnancy. Electronic supplementary material The online version of this article (10.1186/s12940-018-0399-5) contains supplementary material, which is available to authorized users.

Background: Personal care products (PCPs) are exposure sources to phthalates and parabens; however, their contribution to men’s exposure is understudied. Objectives: We examined the association between PCP use and urinary concentrations of phthalate metabolites and parabens in men. Methods: In a prospective cohort, at multiple study visits, men self-reported their use of 14 PCPs and provided a urine sample (2004–2015, Boston, MA). We measured urinary concentrations of 9 phthalate metabolites and methylparaben, propylparaben, and butylparaben. We estimated the covariate-adjusted percent change in urinary concentrations associated with PCP use using linear mixed and Tobit mixed regressions. We also estimated weights for each PCP in a weighted binary score regression and modeled the resulting composite weighted PCP use. Results: Four hundred men contributed 1,037 urine samples (mean of 3/man). The largest percent increase in monoethyl phthalate (MEP) was associated with use of cologne/perfume (83%, p-value<0.01) and deodorant (74%, p-value<0.01). In contrast, the largest percent increase for parabens was associated with the use of suntan/sunblock lotion (66–156%) and hand/body lotion (79–147%). Increases in MEP and parabens were generally greater with PCP use within 6 h of urine collection. A subset of 10 PCPs that were used within 6 h of urine collection contributed to at least 70% of the weighted score and predicted a 254–1,333% increase in MEP and parabens concentrations. Associations between PCP use and concentrations of the other phthalate metabolites were not statistically significant. Conclusions: We identified 10 PCPs of relevance and demonstrated that their use within 6 h of urine collection strongly predicted MEP and paraben urinary concentrations. https://doi.org/10.1289/EHP1374