Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-19 (of 19 Records) |
Query Trace: Gaskins AJ[original query] |
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Cumulative live birth rates following assisted reproduction: the younger, the better? A response
Gaskins AJ , Zhang Y , Kissin DM . Am J Obstet Gynecol 2024 230 (3) |
In-utero exposure to polybrominated biphenyl (PBB) and menstrual cycle function in adulthood
Barat S , Hood RB , Terrell ML , Howards PP , Spencer JB , Wainstock T , Barton H , Pearson M , Kesner JS , Meadows JW , Marcus M , Gaskins AJ . Int J Hyg Environ Health 2023 256 114297 BACKGROUND: There is evidence that in-utero exposure to PBBs, and similar chemicals, are associated with several adverse reproductive health outcomes including altered pubertal timing. However, less is known about the effects of in-utero exposure to PBBs on menstrual cycle function and reproductive hormone levels in adulthood. METHODS: For this menstrual cycle study, we recruited reproductive-aged women in the Michigan PBB Registry who were not pregnant, lactating, or taking hormonal medications (2004-2014). A total of 41 women who were born after the PBB contamination incident (1973-1974) and were prenatally exposed to PBBs, were included in this analysis. We estimated in-utero PBB exposure using maternal serum PBB measurements taken after exposure and extrapolated to time of pregnancy using a PBB elimination model. Women were followed for up to 6 months during which they provided daily urine samples and completed daily diaries. The urine samples were assayed for estrone 3-glucuronide (E(1)3G), pregnanediol 3-glucuronide (Pd3G), and follicle stimulating hormone (FSH). RESULTS: Women in our study were, on average, 27.5 (SD:5.3) years old and contributed 4.9 (SD:1.9) menstrual cycles of follow-up. Compared to women with low in-utero PBB exposure (≤1 ppb), women with medium (>1.0-3.0 ppb) and high (>3.0 ppb) exposure had higher maximum 3-day mean Pd3G levels during the luteal phase. Specifically, the age- and creatinine-adjusted maximum 3-day mean luteal phase Pd3G levels (95% CI) in increasing categories of in-utero PBB exposure were 9.2 (4.6,13.9), 14.8 (11.6,18.0), and 16.1 (12.9,19.3) μg/mg creatinine. There were no meaningful differences in average cycle length, follicular or luteal phase cycle length, bleed length, or creatinine-adjusted E(1)3G or FSH levels by category of in-utero PBB exposure. CONCLUSION: Higher exposure to PBB in-utero was associated with increased progesterone levels across the luteal phase, however, most other menstrual cycle characteristics were largely unassociated with in-utero PBB exposure. Given our modest sample size, our results require cautious interpretation. |
Predicted probabilities of live birth following assisted reproductive technology using United States national surveillance data from 2016-2018
Gaskins AJ , Zhang Y , Chang J , Kissin DM . Am J Obstet Gynecol 2023 228 (5) 557 e1-557 e10 BACKGROUND: As the use of in vitro fertilization (IVF) continues to increase in the US, up-to-date models that estimate cumulative live birth rates following multiple oocyte retrievals and embryo transfers (fresh and frozen) are valuable for patients and clinicians weighing treatment options. OBJECTIVE: To develop models that generate predicted probabilities of live birth in individuals considering IVF based on demographic and reproductive characteristics. STUDY DESIGN: Our population-based cohort study utilized data from the National Assisted Reproductive Technology Surveillance System 2016-2018, including 196,916 women who underwent 207,766 autologous embryo transfer cycles and 25,831 women who underwent 36,909 donor oocyte transfer cycles. We used data on autologous IVF cycles to develop models that estimate a patient's cumulative live birth rate (CLBR) following all embryo transfers (fresh and frozen) within 12 months after one, two, and three oocyte retrievals in new and returning patients. Among patients using donor oocytes, we estimated CLBR after their first, second, and third embryo transfers. Multinomial logistic regression models adjusted for age, pre-pregnancy body mass index (BMI, imputed for 18% of missing values), parity, gravidity, and infertility diagnoses were used to estimate CLBR. RESULTS: Among new and returning patients undergoing autologous IVF, female age had the strongest association with CLBR. Other factors associated with higher CLBRs were lower BMI and parity or gravidity ≥1 although results were inconsistent. Infertility diagnoses of diminished ovarian reserve, uterine factor, and other reasons were associated with lower CLBR while male factor, tubal factor, ovulatory disorders, and unexplained infertility were associated with higher CLBR. Based on our models, a new patient who is 35 years, with a BMI of 25 kg/m(2), no previous pregnancies, and unexplained infertility diagnoses has a 48%, 69%, and 80% CLBR following first, second, and third oocyte retrieval. CLBRs are 29%, 48%, 62% respectively if the patient had diminished ovarian reserve; and 25%, 41%, and 52% if the patient was 40 years (with unexplained infertility). Very few recipient characteristics were associated with CLBR in donor oocyte patients. CONCLUSIONS: Our models provide estimates of CLBR based on demographic and reproductive characteristics to help inform patients and providers of a woman's likelihood of success following IVF. |
Occupational exposure to high-level disinfectants and risk of miscarriage among nurses
Ding M , Lawson C , Johnson C , Rich-Edwards J , Gaskins AJ , Boiano J , Henn S , Rocheleau C , Chavarro JE . Occup Environ Med 2021 78 (10) 731-737 OBJECTIVES: To examine the association of occupational exposure to high-level disinfectants (HLDs) with risk of miscarriage among nurses. METHODS: Our study included women who enrolled in the Nurses' Health Study 3 (2010-2020) and had at least one pregnancy during follow-up. Occupational exposure to HLDs was self-reported at baseline. Every 6 months, a follow-up questionnaire was sent to participants asking for detailed information on pregnancies. We used a discrete-time Cox model to calculate the HRs and 95% CIs of miscarriage according to exposure to HLDs. RESULTS: Our study included 2579 nurses with a median of 5.6 years of follow-up (range: 1-9 years), and we documented 768 (19%) cases of miscarriage among 3974 pregnancies. Compared with women with no HLD exposure, the HRs of miscarriage were 1.08 (95% CI: 0.87 to 1.34) for past users and 0.84 (95% CI: 0.68 to 1.04) for HLD users. Compared with women with no HLD exposure, duration, frequency, and type of HLD and use of exposure controls were not associated with risk of miscarriage. When restricting to pregnancies that occurred within 12 months of HLD use, occupational exposure to unspecified types of HLD was significantly associated with higher risk of miscarriage (HR=1.78; 95% CI: 1.08 to 2.93). CONCLUSIONS: We observed no associations between occupational use of HLDs and miscarriage, except when we restricted to pregnancies occurring within 12 months of assessed baseline exposure. Given the observational design and limited sample size, results should be interpreted cautiously. |
Occupational use of high-level disinfectants and asthma incidence in early- to mid-career female nurses: a prospective cohort study
Dumas O , Gaskins AJ , Boggs KM , Henn SA , Le Moual N , Varraso R , Chavarro JE , Camargo CA Jr . Occup Environ Med 2021 78 (4) 244-247 OBJECTIVES: Occupational use of disinfectants among healthcare workers has been associated with asthma. However, most studies are cross-sectional, and longitudinal studies are not entirely consistent. To limit the healthy worker effect, it is important to conduct studies among early- to mid-career workers. We investigated the prospective association between use of disinfectants and asthma incidence in a large cohort of early- to mid-career female nurses. METHODS: The Nurses' Health Study 3 is an ongoing, prospective, internet-based cohort of female nurses in the USA and Canada (2010-present). Analyses included 17 280 participants without a history of asthma at study entry (mean age: 34 years) and who had completed ≥1 follow-up questionnaire (sent every 6 months). Occupational use of high-level disinfectants (HLDs) was evaluated by questionnaire. We examined the association between HLD use and asthma development, adjusted for age, race, ethnicity, smoking status and body mass index. RESULTS: During 67 392 person-years of follow-up, 391 nurses reported incident clinician-diagnosed asthma. Compared with nurses who reported ≤5 years of HLD use (89%), those with >5 years of HLD use (11%) had increased risk of incident asthma (adjusted HR (95% CI), 1.39 (1.04 to 1.86)). The risk of incident asthma was elevated but not statistically significant in those reporting >5 years of HLD use and current use of ≥2 products (1.72 (0.88 to 3.34)); asthma risk was significantly elevated in women with >5 years of HLD use but no current use (1.46 (1.00 to 2.12)). CONCLUSIONS: Occupational use of HLDs was prospectively associated with increased asthma incidence in early- to mid-career nurses. |
Paternal mixtures of urinary concentrations of phthalate metabolites, bisphenol A and parabens in relation to pregnancy outcomes among couples attending a fertility center
Mínguez-Alarcón L , Bellavia A , Gaskins AJ , Chavarro JE , Ford JB , Souter I , Calafat AM , Hauser R , Williams PL . Environ Int 2020 146 106171 BACKGROUND: Few epidemiologic studies have evaluated the impact of paternal environmental exposures, particularly as mixtures, on couples' pregnancy outcomes. OBJECTIVE: We investigated whether mixtures of paternal urinary bisphenol A (BPA), paraben, and phthalates were associated with pregnancy outcomes among couples attending a fertility center. METHODS: We included 210 couples undergoing 300 in vitro fertilization (IVF) between 2004 and 2017 in this prospective analysis. We quantified paternal urinary biomarker concentrations in one sample per cycle using isotope-dilution tandem mass spectrometry. We used principal component analysis (PCA) to identify correlations of biomarker concentrations and multivariable Cox proportional hazards models for discrete survival time to estimate the hazard ratios (HRs) and 95% CIs for the associations between PCA-derived factor scores and probability of failing to achieve a live birth. Interactions were also included in the models to examine strength of associations over three vulnerable periods [embryo transfer to implantation, implantation to clinical pregnancy, and clinical pregnancy to live birth]. Models were adjusted for paternal and maternal ages and body mass indexes, urinary dilution (specific gravity) and year of collection, infertility diagnosis, and other PCA factor scores. Sensitivity analyses with further adjustment for maternal PCA factor scores were performed. RESULTS: We identified three factors, representing di-2-ethylhexyl phthalate (DEHP) metabolites, BPA and non-DEHP metabolites, and parabens, accounting for 56%, 15% and 10%, respectively, of the total variance explained. An interquartile range (25th and 75th percentiles) increase in the DEHP-related factor score was associated with elevated probability of failing prior to live birth (HR = 1.41, 95% CI: 1.08, 1.81) and the association was stronger between implantation and clinical pregnancy as well as between clinical pregnancy and live birth compared to before implantation. The overall HRs of failure for the BPA/non-DEHP-related and paraben-related factor scores were HR = 1.24 (95% CI: 0.97, 1.59) and HR = 0.99 (95% CI: 0.80, 1.24). We found similar HRs when additionally adjusting for maternal PCA factor scores. CONCLUSION: Paternal mixtures of urinary concentrations of DEHP metabolites were related to higher infertility treatment failure. |
Administration of antineoplastic drugs and fecundity in female nurses
Nassan FL , Lawson CC , Gaskins AJ , Johnson CY , Boiano JM , Rich-Edwards JW , Chavarro JE . Am J Ind Med 2019 62 (8) 672-679 BACKGROUND: We examined the association between the administration of antineoplastic drugs (AD) and fecundity among female nurses. METHODS: AD administration and use of exposure controls (EC) such as gloves, gowns, and needleless systems were self-reported at baseline among 2649 participants of the Nurses' Health Study 3, who were actively attempting pregnancy. Every 6 months thereafter, the nurses reported the current duration of their pregnancy attempt. Multivariable accelerated failure time models were used to estimate time ratios (TR) and 95% confidence intervals (CI) adjusted for age, race, body mass index, smoking, marital status, hours of work, and other occupational risk factors. RESULTS: Mean (standard deviation) age and BMI at baseline were 30.7 years (4.7) and 26.0 kg/m(2) (6.4). Forty-one percent of nurses reported ever administering AD; 30% only in the past and 11% currently. The former administration of AD (TR = 1.02, 95% CI, 0.93-1.12) was unrelated to the ongoing duration of pregnancy attempt. Among nurses currently administering AD, those who had administered AD for 6 years and above had a 27% (95% CI, 6%-53%) longer duration of pregnancy attempt than nurses who never handled ADs in unadjusted analyses. This difference disappeared in multivariable analyses (TR = 1.01, 95% CI, 0.85-1.21). 93% (n = 270) of the nurses currently administering ADs reported consistent use of EC. These nurses had a similar median duration of pregnancy attempt to those who never handled AD (TR = 1.00, 95% CI, 0.87-1.15). CONCLUSIONS: Administration of ADs did not appear to have an impact on fecundity in a cohort of nurses planning for pregnancy with a high prevalence of consistent ECs. Our results may not be generalizable to women who are less compliant with PPE use or with less availability to ECs. Therefore, it is possible that we did not observe an association between occupational exposure to AD and reduced fecundity because of lower exposure due to the more prevalent use of effective ECs. |
Urinary concentrations of bisphenol A, parabens and phthalate metabolite mixtures in relation to reproductive success among women undergoing in vitro fertilization
Minguez-Alarcon L , Messerlian C , Bellavia A , Gaskins AJ , Chiu YH , Ford JB , Azevedo AR , Petrozza JC , Calafat AM , Hauser R , Williams PL . Environ Int 2019 126 355-362 BACKGROUND: We have previously investigated whether urinary concentrations of bisphenol A (BPA), parabens, and phthalate metabolites were individually associated with reproductive outcomes among women undergoing in vitro fertilization (IVF) treatment. However, humans are typically exposed to many man-made chemicals simultaneously. Thus, investigating one chemical at a time may not represent the effect of mixtures. OBJECTIVE: To investigate whether urinary concentrations of BPA, parabens, and phthalate metabolite mixtures are associated with reproductive outcomes among women undergoing IVF. METHODS: This prospective cohort study included 420 women contributing 648 IVF cycles who provided up to two urine samples per cycle prior to oocyte retrieval (N=1145) between 2006 and 2017 at the Massachusetts General Hospital Fertility Center, and had available urine biomarker data. Urinary concentrations of BPA, parabens, and phthalate metabolites were quantified using isotope-dilution tandem mass spectrometry. Intermediate and clinical end-points of IVF treatments were abstracted from electronic medical records. Principal component analysis (PCA) and Bayesian kernel machine regression (BKMR) were used to identify main patterns of BPA, parabens, and phthalate metabolites concentrations. We used generalized linear mixed models to evaluate the association between PCA-derived factor scores, in quartiles, and IVF outcomes, using random intercepts to account for multiple IVF cycles and adjusting for known confounders. Because of temporal trends in exposure, we conducted a sensitivity analysis restricted to women who underwent IVF cycles in the earlier years of study (2006-2012). RESULTS: Urinary concentrations of BPA, parabens, and most phthalate metabolites were significantly lower during the second half of the study period (2013-2017) than during the first half (2006-2012). None of the three factors derived from the PCA [di(2-ethylhexyl) phthalate (DEHP), non-DEHP, and paraben] was associated with IVF outcomes in the main analyses. Similarly, BKRM analyses did not identify any associations of individual urinary concentrations of BPA, paraben and phthalate metabolites with IVF outcomes while accounting for correlation between exposures. However, in sensitivity analyses restricted to women who underwent IVF cycles from 2006 to 2012, where concentrations of most phthalates and phenols were higher, there were decreases in implantation, clinical pregnancy, and live birth across quartiles of the DEHP factor. Specifically, women in the highest quartile of the DEHP factor had, on average, lower probabilities of implantation (-22% p, trend=0.08), clinical pregnancy (-24% p, trend=0.14), and live birth (-38% p, trend=0.06) compared to women in the lowest quartile. Among this group of women, BKMR results did not identify any single contributor driving the decreased probabilities of live birth within the DEHP factor. CONCLUSIONS: We confirmed that women undergoing IVF are concurrently exposed to multiple endocrine disrupting chemicals (EDCs). While we found no overall significant associations, we observed diminished pregnancy success with specific clusters of chemicals among women who underwent IVF cycles in earlier years of study, when urinary concentrations of these EDCs were higher. |
Correlation and temporal variability of urinary biomarkers of chemicals among couples: Implications for reproductive epidemiological studies
Nassan FL , Williams PL , Gaskins AJ , Braun JM , Ford JB , Calafat AM , Hauser R . Environ Int 2018 123 181-188 BACKGROUND: Exposure to some environmental chemicals is ubiquitous and linked to a variety of adverse outcomes, including children's health. While few studies have assessed the contribution of both male and female exposures to children's health, understanding the patterns of couple's exposure is needed to understand their joint effects. OBJECTIVE: We assessed the correlation patterns between male and female partners' concentrations of 37 environmental chemical biomarkers. We also assessed the temporal reliability of the biomarkers within couples. METHODS: We calculated Spearman pairwise correlations between specific gravity adjusted urinary biomarker concentrations and hair mercury concentrations among 380 couples enrolled in the Environment and Reproductive Health (EARTH) study at the Massachusetts General Hospital Fertility Center (2004-2017). We calculated intra-class correlation coefficients (ICCs) for couple's biomarkers to assess the temporal variability of these exposures within a couple using multiple paired-samples from couples. RESULTS: All biomarkers were positively correlated within couples (range: 0.05 for tert-butylphenyl phenyl phosphate to 0.66 for triclosan). In general, the biomarkers with the highest within couple correlation were those of chemicals for which diet (e.g., di(2-ethylhexyl) phthalate), personal care products use (e.g., triclosan, benzophenone-3), and the indoor environment (e.g., 2,5-dichlorophenol) are considered primary exposure sources. Most other biomarkers were moderately correlated (0.3-<0.6). Similar patterns of temporal reliability were observed across biomarkers. CONCLUSIONS: Urinary concentrations of several biomarkers were mostly moderately correlated within couples, suggesting similar exposure sources. Future epidemiological studies should collect samples from both partners to be able to accurately determine the contribution of maternal and paternal exposures to offspring health. |
The Environment and Reproductive Health (EARTH) Study: A prospective preconception cohort
Messerlian C , Williams PL , Ford JB , Chavarro JE , Minguez-Alarcon L , Dadd R , Braun JM , Gaskins AJ , Meeker JD , James-Todd T , Chiu YH , Nassan FL , Souter I , Petrozza J , Keller M , Toth TL , Calafat AM , Hauser R . Hum Reprod Open 2018 2018 (2) Background: The Environment and Reproductive Health (EARTH) Study is an ongoing prospective preconception cohort designed to investigate the impact of environmental, nutritional, and lifestyle factors among both women and men on fertility and pregnancy outcomes. Methods: The EARTH Study recruits women 18 to 45 years and men 18 to 55 years seeking fertility evaluation and treatment at the Massachusetts General Hospital (MGH) Fertility Center, Boston, USA. Women and men are eligible to join either independently or as a couple. Participants are followed from study entry throughout each fertility treatment cycle, once per trimester of pregnancy (for those achieving pregnancy), and up to labor and delivery, or until they discontinue treatment or withdraw from the study. The study collects biological samples, self-reported questionnaire data (including a food frequency questionnaire) and clinically abstracted information. Results: As of June 2017, the study cohort included 799 women and 487 men (447 couples; 40 men joined without female partners). Women were on average 34.7 years old at time of enrolment and predominantly Caucasian (81%), educated (49% have a graduate degree), and nulliparous (83%). Men were on average 36.6 years at baseline and mostly Caucasian (86%) and never-smokers (67%). Conclusions: The EARTH Study is one of the few cohorts designed to examine multiple potentially critical windows of vulnerability, including the paternal and maternal preconception windows and the periconception and prenatal windows in pregnancy. It is also one of the few human studies that has assessed potential interactions between environmental exposures and dietary factors. |
Urinary concentrations of biomarkers of phthalates and phthalate alternatives and IVF outcomes
Machtinger R , Gaskins AJ , Racowsky C , Mansur A , Adir M , Baccarelli AA , Calafat AM , Hauser R . Environ Int 2017 111 23-31 Phthalates are a class of chemicals found in a large variety of consumer products. Available experimental and limited human data show adverse effects of some phthalates on ovarian function, which has raised concerns regarding potential effects on fertility. The aim of the current study was to determine whether urinary concentrations of metabolites of phthalates and phthalate alternatives are associated with intermediate and clinical in vitro fertilization (IVF) outcomes. We enrolled 136 women undergoing IVF in a Tertiary University Affiliated Hospital. Participants provided one to two urine samples per cycle during ovarian stimulation and before oocyte retrieval. IVF outcomes were abstracted from medical records. Concentrations of 17 phthalate metabolites and two metabolites of the phthalate alternative di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) were measured. Multivariable Poisson regression models with log link were used to analyze associations between tertiles of specific gravity adjusted phthalate or DINCH metabolites and number of total oocytes, mature oocytes, fertilized oocytes, and top quality embryos. Multivariable logistic regression models were applied to evaluate the association between tertiles of specific gravity adjusted phthalate or DINCH metabolites and probability of live birth. Urinary concentrations of the sum of di-2-ethylhexyl phthalate metabolites ( summation operatorDEHP) and the individual metabolites mono-2-ethyl-5-hydroxyhexyl phthalate, mono-2-ethyl-5-oxohexyl phthalate, and mono-2-ethyl-5-carboxypentyl phthalate were negatively associated with the number of total oocytes, mature oocytes, fertilized oocytes, and top quality embryos. Of the low molecular weight phthalates, higher monoethyl phthalate and mono-n-butyl phthalate concentrations were associated with significantly fewer total, mature, and fertilized oocytes. None of the urinary phthalate metabolite concentrations were associated with a reduced probability implantation, clinical pregnancy or live birth. Metabolites of DINCH were not associated with intermediate or clinical IVF outcomes. Our results suggest that DEHP may impair early IVF outcomes, specifically oocyte parameters. Additional research is needed to elucidate the potential effect of DEHP on female fertility in the general population. |
Personal care product use in men and urinary concentrations of select phthalate metabolites and parabens: Results from the Environment And Reproductive Health (EARTH) Study
Nassan FL , Coull BA , Gaskins AJ , Williams MA , Skakkebaek NE , Ford JB , Ye X , Calafat AM , Braun JM , Hauser R . Environ Health Perspect 2017 125 (8) 087012 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. |
Occupational use of high-level disinfectants and fecundity among nurses
Gaskins AJ , Chavarro JE , Rich-Edwards JW , Missmer SA , Laden F , Henn SA , Lawson CC . Scand J Work Environ Health 2017 43 (2) 171-180 Objective This study aimed to examine the relationship between occupational use of high-level disinfectants (HLD) and fecundity among female nurses. Methods Women currently employed outside the home and trying to get pregnant (N=1739) in the Nurses' Health Study 3 cohort (2010-2014) were included in this analysis. Occupational exposure to HLD used to disinfect medical instruments and use of protective equipment (PE) was self-reported on the baseline questionnaire. Every six months thereafter women reported the duration of their ongoing pregnancy attempt. Multivariable accelerated failure time models were used to estimate time ratios (TR) and 95% confidence intervals (95% CI). Results Nurses exposed to HLD prior to and at baseline had a 26% (95% CI 8-47%) and 12% (95% CI -2-28%) longer median duration of pregnancy attempt compared to nurses who were never exposed. Among nurses exposed at baseline to HLD, use of PE attenuated associations with fecundity impairments. Specifically, women using 0, 1, and ≥2 types of PE had 18% (95% CI -7-49%), 16% (95% -3-39%), and 0% (95% -22-28%) longer median durations of pregnancy attempt compared to women who were never exposed. While the use of PE varied greatly by type (9% for respiratory protection to 69% for protective gloves), use of each PE appeared to attenuate the associations of HLD exposure with reduced fecundity. Conclusion Occupational use of HLD is associated with reduced fecundity among nurses, but use of PE appears to attenuate this risk. |
Urinary Phthalate Metabolite Concentrations and Reproductive Outcomes among Women Undergoing in Vitro Fertilization: Results from the EARTH Study
Hauser R , Gaskins AJ , Souter I , Smith KW , Dodge LE , Ehrlich S , Meeker JD , Calafat AM , Williams PL . Environ Health Perspect 2016 124 (6) 831-9 BACKGROUND: Evidence from both animal and human studies suggests that exposure to phthalates may be associated with adverse female reproductive outcomes. OBJECTIVE: We evaluated the associations between urinary concentrations of phthalate metabolites and outcomes of assisted reproductive technologies (ART). METHODS: This analysis included 256 women enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2004-2012) who provided one to two urine samples per cycle before oocyte retrieval. We measured 11 urinary phthalate metabolites [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), monocarboxyisooctyl phthalate (MCOP), monocarboxyisononyl phthalate (MCNP), and mono(3-carboxypropyl) phthalate (MCPP)]. We used generalized linear mixed models to evaluate the association of urinary phthalate metabolites with in vitro fertilization (IVF) outcomes, accounting for multiple IVF cycles per woman. RESULTS: In multivariate models, women in the highest as compared with lowest quartile of MEHP, MEHHP, MEOHP, MECPP, ΣDEHP (MEHP + MEHHP + MEOHP + MECPP), and MCNP had lower oocyte yield. Similarly, the number of mature (MII) oocytes retrieved was lower in the highest versus lowest quartile for these same phthalate metabolites. The adjusted differences (95% CI) in proportion of cycles resulting in clinical pregnancy and live birth between women in the fourth versus first quartile of ΣDEHP were -0.19 (-0.29, -0.08) and -0.19 (-0.28, -0.08), respectively, and there was also a lower proportion of cycles resulting in clinical pregnancy and live birth for individual DEHP metabolites. CONCLUSIONS: Urinary concentrations of DEHP metabolites were inversely associated with oocyte yield, clinical pregnancy, and live birth following ART. CITATION: Hauser R, Gaskins AJ, Souter I, Smith KW, Dodge LE, Ehrlich S, Meeker JD, Calafat AM, Williams PL, for the EARTH Study Team. 2016. Urinary phthalate metabolite concentrations and reproductive outcomes among women undergoing in vitro fertilization: results from the EARTH study. Environ Health Perspect 124:831-839; http://dx.doi.org/10.1289/ehp.1509760. |
Dietary folate intake and modification of the association of urinary bisphenol A concentrations with in vitro fertilization outcomes among women from a fertility clinic
Minguez-Alarcon L , Gaskins AJ , Chiu YH , Souter I , Williams PL , Calafat AM , Hauser R , Chavarro JE . Reprod Toxicol 2016 65 104-112 Experimental data in rodents suggest that the effects of bisphenol A (BPA) on oocyte development may be modified by dietary methyl donors. Whether the same interaction exists in humans is unknown. We evaluated whether intake of methyl donors modified the associations between urinary BPA concentrations and treatment outcomes among 178 women who underwent 248 IVF cycles at a fertility center in Boston between 2007 and 2012. Participants completed a validated food frequency questionnaire and provided up to two urine samples per treatment cycle. High urinary BPA concentrations were associated with a 66% lower probability of implantation (p=0.007) among women who consumed <400mug/day of food folate, but not among women consuming ≥400mug/day (21% higher probability of implantation, p=0.18) (p,interaction=0.04). A similar pattern was observed for probability of clinical pregnancy (p,interaction=0.07) and live birth (p,interaction=0.16). These results are consistent with previous animal data but further evaluation in other human populations is needed. |
Soy intake modifies the relation between urinary bisphenol A concentrations and pregnancy outcomes among women undergoing assisted reproduction
Chavarro JE , Minguez-Alarcon L , Chiu YH , Gaskins AJ , Souter I , Williams PL , Calafat AM , Hauser R . J Clin Endocrinol Metab 2016 101 (3) jc20153473 CONTEXT: Experimental data in rodents suggest that the adverse reproductive health effects of bisphenol A (BPA) can be modified by intake of soy phytoestrogens. Whether the same is true in humans is not known. OBJECTIVE: The purpose of this study was to evaluate whether soy consumption modifies the relation between urinary BPA levels and infertility treatment outcomes among women undergoing assisted reproduction. SETTING: The study was conducted in a fertility center in a teaching hospital. DESIGN: We evaluated 239 women enrolled between 2007 and 2012 in the Environment and Reproductive Health (EARTH) Study, a prospective cohort study, who underwent 347 in vitro fertilization (IVF) cycles. Participants completed a baseline questionnaire and provided up to 2 urine samples in each treatment cycle before oocyte retrieval. IVF outcomes were abstracted from electronic medical records. We used generalized linear mixed models with interaction terms to evaluate whether the association between urinary BPA concentrations and IVF outcomes was modified by soy intake. MAIN OUTCOME MEASURE: Live birth rates per initiated treatment cycle were measured. RESULTS: Soy food consumption modified the association of urinary BPA concentration with live birth rates (P for interaction = .01). Among women who did not consume soy foods, the adjusted live birth rates per initiated cycle in increasing quartiles of cycle-specific urinary BPA concentrations were 54%, 35%, 31%, and 17% (P for trend = .03). The corresponding live birth rates among women reporting pretreatment consumption of soy foods were 38%, 42%, 47%, and 49% (P for trend= 0.35). A similar pattern was found for implantation (P for interaction = .02) and clinical pregnancy rates (P for interaction = .03) per initiated cycle, where urinary BPA was inversely related to these outcomes among women not consuming soy foods but unrelated to them among soy consumers. CONCLUSION: Soy food intake may protect against the adverse reproductive effects of BPA. As these findings represent the first report suggesting a potential interaction between soy and BPA in humans, they should be further evaluated in other populations. |
Urinary phthalate metabolites and ovarian reserve among women seeking infertility care
Messerlian C , Souter I , Gaskins AJ , Williams PL , Ford JB , Chiu YH , Calafat AM , Hauser R . Hum Reprod 2015 31 (1) 75-83 STUDY QUESTION: Are urinary phthalate metabolites associated with reduced antral follicle growth among women in an infertility setting? SUMMARY ANSWER: Higher urinary concentrations of di(2-ethylhexyl) phthalate (DEHP) metabolites were associated with significant decreases in antral follicle count (AFC) among women seeking infertility care. WHAT IS KNOWN ALREADY: Experimental animal studies show that DEHP accelerates primordial follicle recruitment and inhibits antral follicle growth. Whether phthalates also reduce the growing antral follicle pool in humans remains unknown. STUDY DESIGN, SIZE, DURATION: We examined the association between urinary phthalate metabolites and AFC using prospective data from 215 females recruited between 2004 and 2012 in the Environment and Reproductive Health (EARTH) study. PARTICIPANTS/MATERIALS, SETTING, METHODS: We quantified the urinary concentrations of 11 phthalate metabolites. We estimated the geometric mean for all urine samples provided prior to unstimulated day 3 AFC assessment for each woman. We evaluated the association of AFC with summation operatorDEHP (molar sum of four DEHP metabolites) and individual phthalate metabolites using Poisson regression, adjusting for age, BMI and smoking. MAIN RESULTS AND THE ROLE OF CHANCE: We observed significant decreases in mean AFC for all higher quartiles of summation operatorDEHP as compared with the lowest quartile. Compared with women in the first quartile of summation operatorDEHP, women in the second, third and fourth quartiles had a -24% (95% confidence interval (CI): -32%, -16%), -19% (95% CI: -27%, -9%), and -14% (95% CI: -23%, -5%) decrease in mean AFC. The absolute mean AFC in the first quartile was 14.2 follicles (95% CI: 13.2, 15.2) compared with 10.7 follicles (95% CI: 9.9, 11.6) in the second quartile. We observed similar trends among the four individual DEHP metabolites. There was no consistent change in AFC among the remaining phthalate metabolite concentrations evaluated. LIMITATIONS, REASONS FOR CAUTION: We demonstrated a negative association between DEHP and a well-established marker of ovarian reserve among a subfertile population. However these findings may not be generalizable to women without fertility concerns, and we cannot rule out co-exposure to other chemicals. WIDER IMPLICATIONS OF THE FINDINGS: Environmental chemicals that inhibit the size of the growing antral follicle pool can impair fertility and reduce fecundity. This study suggests evidence in need of further investigation on the impact of phthalates on the human oocyte and follicular development. STUDY FUNDING/COMPETING INTERESTS: Work supported by grants ES009718, ES022955, ES000002, and T32ES007069 from the National Institute of Environmental Health Sciences (NIEHS) and grant T32 DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). C.M. was supported by a post-doctoral training award from the Canadian Institutes of Health Research. There are no competing interests to declare. |
Work schedule and physical factors in relation to fecundity in nurses
Gaskins AJ , Rich-Edwards JW , Lawson CC , Schernhammer ES , Missmer SA , Chavarro JE . Occup Environ Med 2015 72 (11) 777-83 OBJECTIVES: To evaluate the association of work schedule and physical factors with fecundity. METHODS: Women currently employed outside the home and trying to get pregnant (n=1739) in the Nurses' Health Study 3 cohort (2010-2014) were included in this analysis. Work schedule and physical labour were self-reported on the baseline questionnaire, and every 6 months thereafter the women reported the duration of their ongoing pregnancy attempt. Multivariable accelerated failure time models were used to estimate time ratios (TR) and 95% CIs. RESULTS: Among the 1739 women (median age=33 years, 93% Caucasian) the estimated proportions of women not pregnant after 12 and 24 months were 16% and 5%, respectively. None of the various shift work patterns were associated with duration of pregnancy attempt (as a surrogate for fecundity). However, women working >40 h/week had a 20% (95% CI 7 to 35%) longer median duration of pregnancy attempt compared to women working 21-40 h/week (p-trend=0.005). Women whose work entailed heavy lifting or moving (ie, 25+ pounds) >15 times/day also had a longer median duration of pregnancy attempt (adjusted TR=1.49; 95% CI 1.20 to 1.85) compared to women who never lifted or moved heavy loads (p-trend=0.002). The association between heavy moving and lifting and duration of pregnancy attempt was more pronounced among overweight or obese women (body mass index, BMI<25: TR=1.17; 95% CI 0.88 to 1.56; BMI≥25: TR=2.03, 95% CI 1.48 to 2.79; p-interaction=0.007). CONCLUSIONS: Working greater than 40 h per week and greater frequency of lifting or moving a heavy load were associated with reduced fecundity in a cohort of nurses planning pregnancy. |
Urinary bisphenol A concentrations and association with in vitro fertilization outcomes among women from a fertility clinic
Minguez-Alarcon L , Gaskins AJ , Chiu YH , Williams PL , Ehrlich S , Chavarro JE , Petrozza JC , Ford JB , Calafat AM , Hauser R . Hum Reprod 2015 30 (9) 2120-8 STUDY QUESTION: Are urinary BPA concentrations associated with in vitro fertilization (IVF) outcomes among women attending an academic fertility center? SUMMARY ANSWER: Urinary BPA concentrations were not associated with adverse reproductive and pregnancy outcomes among women from a fertility clinic. WHAT IS KNOWN ALREADY: Bisphenol A (BPA), an endocrine disruptor, is detected in the urine of most Americans. Although animal studies have demonstrated that BPA reduces female fertility through effects on the ovarian follicle and uterus, data from human populations are scarce and equivocal. STUDY DESIGN, SIZE AND DURATION: This prospective cohort study between 2004 and 2012 at the Massachusetts General Hospital Fertility Center included 256 women (n = 375 IVF cycles) who provided up to two urine samples prior to oocyte retrieval (total N = 673). PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Study participants were women enrolled in the Environment and Reproductive Health (EARTH) Study. Intermediate and clinical end-points of IVF treatments were abstracted from electronic medical records. We used generalized linear mixed models with random intercepts to evaluate the association between urinary BPA concentrations and IVF outcomes adjusted by age, race, body mass index, smoking status and infertility diagnosis. MAIN RESULTS AND THE ROLE OF CHANCE: The specific gravity-adjusted geometric mean of BPA was 1.87 microg/l, which is comparable to that for female participants in the National Health and Nutrition Examination Survey, 2011-2012. Urinary BPA concentrations were not associated with endometrial wall thickness, peak estradiol levels, proportion of high quality embryos or fertilization rates. Furthermore, there were no associations between urinary BPA concentrations and implantation, clinical pregnancy or live birth rates per initiated cycle or per embryo transfer. Although we did not find any associations between urinary BPA concentrations and IVF outcomes, the relation between BPA and endometrial wall thickness was modified by age. Younger women (<37 years old) had thicker endometrial thickness across increasing quartiles of urinary BPA concentrations, while older women (≥37 years old) had thinner endometrial thickness across increasing quartiles of urinary BPA concentrations. LIMITATIONS, REASONS FOR CAUTION: Limitations to this study include a possible misclassification of BPA exposure and difficulties in extrapolating the findings to the general population. WIDER IMPLICATIONS OF THE FINDINGS: Data on the relation between urinary BPA concentrations and reproductive outcomes remain scarce and additional research is needed to clarify its role in human reproduction. STUDY FUNDING/COMPETING INTERESTS: This work was supported by NIH grants R01ES022955, R01ES009718 and R01ES000002 from the National Institute of Environmental Health Sciences (NIEHS) and grant T32DK00770316 from the National Institute of Child Health and Human Development (NICHD). None of the authors has any conflicts of interest to declare. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. |
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