Paternal urinary concentrations of organophosphate flame retardant metabolites, fertility measures, and pregnancy outcomes among couples undergoing in vitro fertilization. (February 2018)

• Record Type: Journal Article
• Authors: Carignan, Courtney C.; Mínguez-Alarcón, Lidia; Williams, Paige L.; Meeker, John D.; Stapleton, Heather M.; Butt, Craig M.; Toth, Thomas L.; Ford, Jennifer B.; Hauser, Russ
• Is Part Of: Environment international. Volume 111(2018)
• Page Start: 232
• Page End: 238
• Publication Date: 2018-02
• Subjects: ART assisted reproductive technologies -- BCIPP bis(1-chloro-2-propyl) phosphate -- BDCIPP bis(1, 3-dichloro-2-propyl) phosphate -- BMI body mass index -- CI confidence interval -- DPHP diphenyl phosphate -- EARTH Environment and Reproductive Health Study -- GM geometric mean -- GnRH gonadotropin releasing hormone -- ICC intraclass correlation coefficients -- ip-PPP isopropylphenyl phenyl phosphate -- IQR interquartile range -- IVF in vitro fertilization -- LC-MS/MS liquid chromatography tandem mass spectrometry -- MDL method detection limits -- MGH Massachusetts General Hospital -- Mono-ITP mono-substituted isopropyl triphenyl phosphate -- PFR organophosphate flame retardant -- SG specific gravity -- SRM standard reference material -- tb-PPP tert-butylphenyl phenyl phosphate -- TDCIPP tris(1, 3-dichloro-2-propyl) phosphate -- TPHP triphenyl phosphate; Endocrine disruption -- Epidemiology -- Fertility -- Flame retardants -- Reproductive health; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2017.12.005
• Languages: English
• ISSNs: 0160-4120

Abstract

Abstract: Background: 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. Methods: 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. Results: 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). Conclusions: 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. Graphical abstract: Highlights: Preconception cohort of couples undergoing IVF as a model of human reproduction Measured concentrations of urinary organophosphate flame retardant metabolites No associations were observed for implantation, clinical pregnancy, or live birth. Fertilization declined with increasing paternal exposure to TDCIPP.