Adverse effects of phthalates on ovarian response to IVF

London, 8 July 2013: Phthalates are among a group of industrial chemicals shown in somestudies to have adverse effects on reproductive health and development, particularly in themale. As such, they have been collectively defined as "endocrine disruptors", and proposed asone of several possible environmental exposures responsible for a decline in fertility. They areclassified in two groups - high molecular weight phthalates are used in the production ofplastics, while low molecular weight phthalates are frequently used in the manufacture ofcosmetics.(1) Human studies increasingly report associations of phthalates with various adversereproductive outcomes, including altered semen quantity and quality.Their effect, however, has been less well studied in women, and, despite widespread humanexposure to phthalates, little is known about the effects of low-level, daily exposures tophthalates on ovarian function - and hence on women's reproductive health.

A new study reported at this year's annual meeting of ESHRE by Dr Irene Souter ofMassachusetts General Hospital and Harvard Medical School in Boston, USA, now suggests thatexposure to phthalates - as measured by levels of phthalate metabolites in urine - is associatedwith reduced fertility when defined as a response to IVF treatment. " Our data support thehypothesis that exposure to specific phthalates might lead to adverse female reproductiveoutcomes," said Dr Souter.

The study followed the progress of 231 women (in 325 fresh treatment cycles) scheduled forIVF at the Massachusetts General Hospital between 2004 and 2012; urine samples were taken atthe start of and throughout treatment and analysed for metabolites of four primary phthalates.

The association of levels of urinary metabolites was then explored with three markers ofresponse to IVF: the number of eggs produced following ovarian stimulation, embryodevelopment, and implantation failure.

Results first showed that urinary phthalates were detected in almost all the women, reflectingthe widespread level of exposure. Results also showed:

  • The odds of implantation failure increased with each rising quartile of two of the urinaryphthalate metabolites. For example, for DEHP (used in vinyl plastic products) the odds ofimplantation failure in the highest quartile Q4) was twice that of the lowest (Q1).
  • There was also an escalating decrease of 4.17% (Q2), 6.19% (Q3) and 11.4% (Q4) in thenumber of oocytes retrieved with each DEHP phthalate quartile when compared with Q1 (thelowest reference quartile).

The results thus showed that urinary concentrations of some commonly used phthalates were"dose-dependently" associated with a lower yield of IVF oocytes, and an increased risk ofimplantation failure. However, the results did not detect any association between levels ofurinary phthalates and rates of fertilisation or embryo development.

Commenting, Dr Souter believes the results "support the hypothesis" that phthalates arewidespread in the environment and may well have an adverse effect on female fertility,particularly when tested in the model of IVF.

"We are all primarily exposed to phthalates through inhalation and ingestion," she explained. "Itis extremely difficult if not impossible to avoid exposure to phthalates, since they are in so manyproducts." However, she added, exposure can be reduced by the following:

  • Limit the use of personal care products with fragrances in them (including many of the modernbaby care products and air fresheners).
  • Limit use of plastic food storage containers and plastic wraps (certainly do not heat food inthem).
  • Read the labels and avoid children's toys made of plastics (vinyl) that contain phthalates.

Source: European Society of Human Reproduction and Embryology