Urinary metabolites of di(2-ethylhexyl) phthalate are associated with increased risk of implantation failure among women undergoing IVF.
Ehrlich SR; Meeker JD; Williams PL; Wright D; Petrozza J; Hauser R
Fertil Steril 2010 Sep; 94(4)(Suppl 1):S73
OBJECTIVE: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer widely used in consumer products. In rodent studies, MEHP (a metabolite of DEHP) was associated with implantation failure and reduced litter size. We investigated the association between urinary DEHP metabolites and implantation failure in women undergoing IVF. DESIGN: Prospective cohort study among women undergoing IVF at Massachusetts General Hospital Fertility Center. MATERIALS AND METHODS: DEHP metabolites were measured by the CDC using on-line solid phase extraction-high performance liquid chromatography- isotope dilution tandem mass spectrometry. Implantation failure was defined as a negative BHCG test (<6mIU/mL) 2 weeks after embryo transfer. Multivariate models applying a generalized estimating equation (GEE) approach, adjusting for correlation between multiple IVF cycles within the same woman, were used to evaluate the association between quartiles of urinary phthalate metabolite concentration (adjusted for specific gravity) and implantation failure. We adjusted for age, protocol and day of embryo transfer (day 5 versus day 3). RESULTS: Urinary DEHP metabolite concentrations were measured in 79 women (mean age 35.6 yrs) undergoing 96 IVF cycles; 15 women [19 %] had more than 1 IVF cycle. Forty (42%) of the IVF cycles resulted in implantation failure. A significant dose response association was observed between implantation failure and urinary DEHP metabolites, particularly for MEHP (test for trend, p-value=0.002) where odds ratios were 2.05, 3.56 and 7.10 for the second to fourth quartiles of urinary MEHP levels, respectively, as compared to the lowest quartile. Other urinary DEHP metabolites (MEOHP, MEHHP and MECPP) showed similar but slightly weaker patterns of association with implantation failure. CONCLUSION: Among women undergoing IVF, those with higher DEHP metabolite levels, particularly MEHP, had significantly higher risk of uterine implantation failure.
Reproductive-effects; Reproductive-system-disorders; Fertility; Plasticizers; Phthalates; Women; Pregnancy; In-vitro-studies; Metabolites; Urinalysis; Dose-response; Risk-analysis; Risk-factors
Fertility and Sterility
Harvard University, School of Public Health, Boston, Massachusetts