Parental contributions to early embryo development: influences of urinary phthalate and phthalate alternatives among couples undergoing IVF treatment

Abstract

STUDY QUESTION: Are preconception urinary concentrations of phthalates and phthalate alternatives associated with diminished early stage embryo quality in couples undergoing IVF?SUMMARY ANSWER: Male, but not female, urinary concentrations of select metabolites of phthalates and phthalate alternatives are associated with diminished blastocyst quality.WHAT IS KNOWN ALREADY: Although phthalates are endocrine disrupting compounds associated with adverse reproductive health, they are in widespread use across the world. Male and female preconception exposures to select phthalates have been previously associated with adverse reproductive outcomes in both the general population and in those undergoing IVF. STUDY DESIGN, SIZE, DURATION: This prospective cohort included 50 subfertile couples undergoing IVF in western Massachusetts. PARTICIPANTS/MATERIALS, SETTING, METHODS:This study includes the first 50 couples recruited from the Baystate Medical Center's Fertility Center in Springfield, MA, as part of the Sperm Environmental Epigenetics and Development Study (SEEDS). Relevant data from both partners, including embryo quality at the cleavage (Day 3) and blastocyst (Day 5) stages, were collected by clinic personnel during the normal course of an IVF cycle. A spot urine sample was collected from both male and female partners on the same day as semen sample procurement and oocyte retrieval. Concentrations of 17 urinary metabolite were quantified by liquid chromatography mass spectrometry and normalized via specific gravity. Generalized estimating equations were used to estimate odds ratios (OR) and 95% CI, with urinary phthalates and phthalate alternatives fitted as continuous variables and embryo quality as a binary variable. MAIN RESULTS AND THE ROLE OF CHANCE:The 50 couples contributed 761 oocytes, of which 423 progressed to the cleavage stage, 261 were high-quality cleavage stage embryos, 137 were transferrable quality blastocysts and 47 were high-quality blastocysts. At the cleavage stage, male urinary monoethyl phthalate concentrations were positively associated with high-quality cleavage stage embryos (OR = 1.20, 95% CI 1.01-1.43, P = 0.04); no other significant associations were observed at this stage. At the blastocyst stage, male urinary concentrations of monobenzyl phthalate (OR = 0.55, 95% CI 0.36-0.84, P = 0.01), mono-3-hydroxybutyl phthalate (OR = 0.37, 95% CI 0.18-0.76, P = 0.01), mono-n-butyl phthalate (OR = 0.55, 95% CI 0.42-0.73, P < 0.01) and monomethyl phthalate (OR = 0.39, 95% CI 0.26-0.60, P < 0.01) were inversely associated with high-quality blastocysts. A borderline statistically significant relationship was observed for male concentrations of mono (2-ethylhexyl) phthalate (OR = 0.52, 95% CI 0.27-1.00, P = 0.05) and cyclohexane-1,2-dicarboxylic acid-monocarboxy isooctyl ester (OR = 0.21, 95% CI 0.04-1.03, P = 0.05) at the blastocyst stage. Similar inverse associations were observed between male urinary phthalate metabolite concentrations and likelihood of transferrable quality blastocysts. For femal...

Small RNAs in Rat Sperm Are a Predictive and Sensitive Biomarker of Exposure to the Testicular Toxicant Ethylene Glycol Monomethyl Ether

“…The effects of other male reproductive toxicants on embryonic development have been explored. Phthalate metabolites, measured in urine of male clinical subjects, show modest associations with blastocyst quality in assessment of in vitro fertilization (Wu et al, 2017). The results taken together indicate that low-dose EMGE exposures could pose a preconception threat to offspring of exposed fathers.…”

Epigenetics as a Driver of Developmental Origins of Health and Disease: Did We Forget the Fathers?

“…A recent study on American couples undergoing IVF treatment showed an association between paternal exposure to phthalates and poor quality of blastocysts . Here too, a potentially underlying epigenetic mechanism was not further verified.…”

Paternal and maternal urinary phthalate metabolite concentrations and birth weight of singletons conceived by subfertile couples

“…Given that phthalates may exert effects on both gametes and embryos, studies assessing exposure before conception as well as during pregnancy are necessary. Moreover, new and emerging research suggests that the preconception period may be highly sensitive to environmental perturbations and paternal preconception exposure may be an important and largely unexplored determinant of offspring health (Braun et al 2017; Wu et al 2016). Thus, we aimed to investigate whether paternal and maternal preconception and maternal prenatal urinary phthalate metabolite concentrations were associated with infant birth weight using a prospective cohort of couples undergoing treatment in a large fertility center.…”