Urinary concentrations of bisphenol A, parabens and phthalate metabolite mixtures in relation to reproductive success among women undergoing in vitro fertilization.
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.
To investigate whether urinary concentrations of BPA, parabens, and phthalate metabolite mixtures are associated with reproductive outcomes among women undergoing IVF.
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).
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.
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.
Mínguez-Alarcón L
，Messerlian C
，Bellavia A
，Gaskins AJ
，Chiu YH
，Ford JB
，Azevedo AR
，Petrozza JC
，Calafat AM
，Hauser R
，Williams PL
，Earth Study Team
... -
《-》
Associations between paternal urinary phthalate metabolite concentrations and reproductive outcomes among couples seeking fertility treatment.
Limited evidence suggests that male exposure to ubiquitous environmental phthalates may result in poor reproductive outcomes among female partners.
This analysis included male-female couples undergoing in vitro fertilization (IVF) and/or intrauterine insemination (IUI). We evaluated associations between the geometric mean of paternal specific gravity-adjusted urinary phthalate concentrations prior to the female partners' cycle and fertilization, embryo quality, implantation, and live birth using generalized linear mixed models.
Two-hundred eighteen couples underwent 211 IVF and 195 IUI cycles. Trends were observed between paternal urinary mono-3-carboxypropyl phthalate (MCPP; P=0.01) and mono(carboxyoctyl) phthalate (MCOP; P=0.01) and decreased odds of implantation. MCPP and MCOP were also associated with decreased odds of live birth following IVF (P=0.01 and P=0.04, respectively), and monobutyl phthalate above the first quartile was significantly associated with decreased odds of live birth following IUI (P=0.04). However, most urinary phthalate metabolites were not associated with these reproductive outcomes.
Selected phthalates were associated with decreased odds of implantation and live birth.
Dodge LE
，Williams PL
，Williams MA
，Missmer SA
，Souter I
，Calafat AM
，Hauser R
，EARTH Study Team
... -
《-》
Urinary bisphenol A concentrations and association with in vitro fertilization outcomes among women from a fertility clinic.
Are urinary BPA concentrations associated with in vitro fertilization (IVF) outcomes among women attending an academic fertility center?
Urinary BPA concentrations were not associated with adverse reproductive and pregnancy outcomes among women from a fertility clinic.
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.
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).
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.
The specific gravity-adjusted geometric mean of BPA was 1.87 µg/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 to this study include a possible misclassification of BPA exposure and difficulties in extrapolating the findings to the general population.
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.
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.
Mínguez-Alarcón L
，Gaskins AJ
，Chiu YH
，Williams PL
，Ehrlich S
，Chavarro JE
，Petrozza JC
，Ford JB
，Calafat AM
，Hauser R
，EARTH Study Team
... -
《-》
Paternal urinary concentrations of organophosphate flame retardant metabolites, fertility measures, and pregnancy outcomes among couples undergoing in vitro fertilization.
Use of organophosphate flame retardants (PFRs) has increased over the past decade following the phase out of some brominated flame retardants, leading to increased human exposure. We recently reported that increasing maternal PFR exposure is associated with poorer pregnancy outcomes among women from a fertility clinic. Because a small epidemiologic study previously reported an inverse association between male PFR exposures and sperm motility, we sought to examine associations of paternal urinary concentrations of PFR metabolites and their partner's pregnancy outcomes.
This analysis included 201 couples enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2005-2015) who provided one or two urine samples per IVF cycle. In both the male and female partner, 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). The sum of the molar concentrations of the urinary PFR metabolites was calculated. We used multivariable generalized linear mixed models to evaluate the association of urinary concentrations of paternal PFR metabolites with IVF outcomes, accounting for multiple in vitro fertilization (IVF) cycles per couple. Models were adjusted for year of IVF treatment cycle, primary infertility diagnosis, and maternal urinary PFR metabolites as well as paternal and maternal age, body mass index, and race/ethnicity.
Detection rates were high for paternal urinary concentrations of BDCIPP (84%), DPHP (87%) and ip-PPP (76%) but low for tb-PPP (12%) and zero for BCIPP (0%). We observed a significant 12% decline in the proportion of fertilized oocytes from the first to second quartile of male urinary ΣPFR and a 47% decline in the number of best quality embryos from the first to third quartile of male urinary BDCIPP in our adjusted models. An 8% decline in fertilization was observed for the highest compared to lowest quartile of urinary BDCIPP concentrations (95% CI: 0.01, 0.12, p-trend=0.06).
Using IVF as a model to investigate human reproduction and pregnancy outcomes, we found that paternal urinary concentrations of BDCIPP were associated with reduced fertilization. In contrast to previously reported findings for the female partners, the paternal urinary PFR metabolites were not associated with the proportion of cycles resulting in successful implantation, clinical pregnancy, and live birth. These results indicate that paternal preconception exposure to TDCIPP may adversely impact successful oocyte fertilization, whereas female preconception exposure to ΣPFRs may be more relevant to adverse pregnancy outcomes.
Carignan CC
，Mínguez-Alarcón L
，Williams PL
，Meeker JD
，Stapleton HM
，Butt CM
，Toth TL
，Ford JB
，Hauser R
，EARTH Study Team
... -
《-》
ResearchGate
(全网免费下载)
钛学术
(全网免费下载)
