Kate Johnson

October 23, 2015

BALTIMORE — In women who conceive using assisted reproductive technologies, there is an association between pregnancy loss and elevated urinary concentrations of endocrine-disrupting chemicals, known as phthalates, new research indicates.

Phthalates are found in many plastic food and beverage containers, cosmetics, and toys, and can be detected in the urine of more than 95% of the population in the United States, said lead investigator Carmen Messerlian, PhD, from the Harvard T.H. Chan School of Public Health in Boston.

However, the study findings might not be "generalizable to women without fertility concern," Dr Messerlian told Medscape Medical News. Subfertile couples conceiving with medically assisted reproduction may be more sensitive to the adverse effects of endocrine-disrupting chemicals."

Dr Messerlian presented findings from the study, the first to report this adverse association, as a prize paper here at the American Society for Reproductive Medicine 2015 Annual Meeting.


The team used data from the Environmental and Reproductive Health Study (EARTH), a prospective cohort study of couples who received infertility treatment at Massachusetts General Hospital from 2004 to 2012.

In the 256 women involved in the study, there were 303 pregnancies. Of these, 73% used in vitro fertilization and 27% used intrauterine insemination.

Each woman provided two urine samples — one before embryo transfer and one on the day of transfer — which were assessed for four metabolites of di(2-ethylhexly)phthalate at the Centers for Disease Control and Prevention.

Of the 303 pregnancies, 82 (27%) ended before 20 weeks of gestation, and 31 of those were biochemical losses, she reported.

In women with elevated levels of urinary phthalate before conception, there was a two- to threefold increase in the risk for a biochemical pregnancy loss, and a 10% to 60% increase in the risk for loss before 20 weeks.

We can reduce exposure by avoiding plastic dishes and reducing the use of cosmetics.

Specifically, the rate of biochemical pregnancy loss was significantly higher when levels of urinary phthalates were in the highest quartile than when they were in the lowest quartile (17% vs 4%; P < .05).

And the relative risk for biochemical pregnancy loss in the highest quartile of urinary phthalate, compared with the lowest quartile, was 3.4 (P trend = .04), after adjustment for covariates such as age, body mass index, smoking, and infertility diagnosis.

Similarly, loss before 20 weeks of gestation was significantly more common in the highest quartile of urinary phthalate, compared with the lowest (39% vs 23%; P < .05). And in the fully adjusted regression model, the relative risk for total pregnancy loss in the highest quartile, compared with the lowest, was 1.6 (P trend = .06).

"We don't know the mechanism, but some have hypothesized that it affects the egg itself and, therefore, the quality of the embryo, or that it impacts implantation," Dr Messerlian told Medscape Medical News.

Previous research, by Dr Messerlian and others, has demonstrated that antral follicles are significantly depleted in women with higher exposure to phthalates, "so they also have significantly fewer eggs," she added.

Dr Messerlian suggested patients be counseled to be careful about what they consume in the cycle before treatment. "It's a short-lived chemical. It takes 6 to 12 hours to eliminate it from your body," she said.

Although an association between phthalate exposure and pregnancy loss has been reported in women exposed to occupational levels of phthalates, only three studies have reported this association in the general public, and none have reported it in infertile women.

In the general public, the association "is mainly due to the fact that phthalates affect maternal or fetal endocrinology, as well as extravillous trophoblast invasion," senior investigator of the most recent study of the general public, Jianying Hu, PhD, from Peking University in China, told Medscape Medical News (Environ Sci Technol. 2015;49:10651-10657).

She said she agrees that clinicians should advise patients to reduce their phthalate exposure.

"It is difficult to reduce phthalate exposure because of its high production volume, wide usage in our life, and environmental ubiquity," Dr Hu explained. "However, we can reduce exposure by avoiding plastic dishes and reducing the use of cosmetics, which have phthalates."

Dr Messerlian and Dr Hu have disclosed no relevant financial relationships.

American Society for Reproductive Medicine (ASRM) 2015 Annual Meeting: Abstract O-96. October 20, 2015.


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