Organophosphate flame-retardant metabolite concentrations and pregnancy loss among women conceiving with assisted reproductive technology

Abstract

Objective: To evaluate whether urinary concentrations of organophosphate flame retardant (PFR) metabolites are associated with pregnancy loss among women conceiving with assisted reproductive technology (ART). Design: Prospective preconception cohort of subfertile women. Setting: Academic hospital fertility center in Boston, Massachusetts. Patient(s): A total of 155 women conceiving 179 pregnancies with ART. Intervention(s): None. Mean exposure to each of five PFR metabolites was estimated by averaging the specific-gravity adjusted natural log concentrations from two urine samples collected during the ART cycle of conception. Main Outcome Measure(s): Adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for biochemical and total pregnancy loss (all losses <20 weeks' gestation) by quartiles of PFR metabolite concentrations were estimated using a repeated measures log-binomial model, accounting for multiple pregnancies per woman. Result(s): Of the 179 pregnancies, 31% ended in pregnancy loss (12% in biochemical loss). Among the three metabolites with high detection frequency [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), and isopropylphenyl phenyl phosphate (ip-PPP)], an increased risk of biochemical loss was observed for women with DPHP concentrations in the fourth vs. first quartile (RR 1.64; 95% CI 0.61-4.39). Also found was an elevated risk of biochemical pregnancy loss among women in the highest quartile of the molar sum of urinary PFR metabolites compared with the lowest (RR 1.89; 95% CI 0.64-5.58). Urinary concentrations of ip-PPP and BDCIPP were not associated with either outcome. Conclusion(s): Among subfertile women, urinary DPHP metabolite concentrations measured during the ART cycle of conception may be associated with early pregnancy loss. Although this study is uniquely designed to investigate early markers of pregnancy success and maintenance, the small sample size likely contributed to imprecision. Given their increasing use as replacement chemicals for traditional flame retardants, exposure to PFRs may increase, and more studies will be needed to investigate their potential to impact pregnancy and reproduction. (Fertil Steril Ò 2018;110:1137-44. Ó2018 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.

Urinary Organophosphate Metabolite Concentrations and Pregnancy Outcomes among Women Conceiving through in Vitro Fertilization in Shanghai, China

“…Potential confounders were selected from previous studies of environmental pollutant exposures on IVF outcomes (Messerlian et al 2018;Carignan et al 2017;Messerlian et al 2016). The following covariates were included in all models: age, body mass index (BMI), duration of infertility, smoking status, education, annual household income, and infertility diagnosis.…”

“…To evaluate the association between the urinary DAP metabolites concentrations and IVF outcomes, we used generalized estimating equations (GEE) models to account for multiple IVF cycles and end-point outcomes in the same women (Chiu et al 2018, Ehrlich et al 2012Machtinger et al 2013;Mok-Lin et al 2010). The normal distribution and identity link were applied for continuous outcomes (peak E 2 concentration, endometrial thickness), and a binomial distribution and logit link function were specified for fertilization and clinical outcomes (implantation, clinical pregnancy, and live birth) (Machtinger et al 2013;Messerlian et al 2018). Finally, Poisson regression models using a GEE approach were applied for the total number of oocytes and mature MII oocytes as well as best quality embryo (Ehrlich et al 2012;Mok-Lin et al 2010).…”

“…Fifth, we did not consider the male partner's exposure, which may be correlated with his female partner and could contribute and bias the observed association. Last, it is possible that our study results are influenced by uncontrolled confounding provided by unconsidered and possibly important environmental reproductive toxicants, such as phthalate, bisphenol A, and organophosphate FR, which have also been reported to affect IVF outcomes (Messerlian et al 2016;Ehrlich et al 2012;Mok-Lin et al 2010;Messerlian et al 2018). More research in this area is needed to shed more light into the complex interaction between environmental exposure and reproductive outcomes.…”

“…Potential confounders were selected from previous studies of environmental pollutant exposures on IVF outcomes ( Messerlian et al. 2018 ; Carignan et al.…”

Organophosphate toxicity: updates of malathion potential toxic effects in mammals and potential treatments

“…Pesticides are known to induce reproductive toxicity in animals and humans, and many studies have documented the role of pesticides in mediating infertility (Runkle et al 2017;Sifakis et al 2017). The adverse effects of pesticides and OPs were reported to affect the reproductive system of both males and females (Mehrpour et al 2014;Messerlian et al 2018).…”