Urinary Phthalate Metabolite Concentrations and Reproductive Outcomes among Women Undergoing in Vitro Fertilization: Results from the EARTH Study

Russ Hauser, Audrey J Gaskins, Irene Souter, Kristen W Smith, Laura E Dodge, Shelley Ehrlich, John D Meeker, Antonia M Calafat, Paige L Williams, EARTH Study Team, Russ Hauser, Audrey J Gaskins, Irene Souter, Kristen W Smith, Laura E Dodge, Shelley Ehrlich, John D Meeker, Antonia M Calafat, Paige L Williams, EARTH Study Team

Abstract

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.

Conflict of interest statement

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC.

The authors declare they have no actual or potential competing financial interests.

Figures

Figure 1
Figure 1
Overview of in vitro fertilization (IVF) outcomes of 256 women (375 cycles) in the Environment and Reproductive Health Study enrolled between 2004 and 2012. Abbreviations: IUI, intrauterine insemination; IVF, in vitro fertilization; SAB, spontaneous abortion; SB, stillbirth; TAB, therapeutic abortion.
Figure 2
Figure 2
Adjusted mean (95% CI) total, mature (MII), and fertilized oocyte count by quartile of urinary phthalate metabolites and ∑DEHP concentrations among 247 women undergoing 357 IVF cycles with successful egg retrieval: (A) ∑DEHP, (B) MEHP, (C) MEHHP, (D) MEOHP, (E) MECPP, (F) MCOP, (G) MCNP. Adjusted models control for maternal age (continuous), body mass index (continuous), smoking status (never, ever), and primary SART infertility diagnosis at study entry (female, male, unexplained). *p-value for comparison against Q1 < 0.05.

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