BPA diminishes in vitro success.

May 16, 2012

Ehrlich, S, PL Williams, SA Missmer, JA Flaws, KF Berry, A Calafat, X Ye, JC Petrozza, D Wright and R Hauser. 2012. Urinary bisphenol A concentrations and implantation failure among women undergoing in vitro fertilization. Environmental Health Perspectives http://dx.doi.org/10.1289/ehp.1104307.




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Exposure to bisphenol A (BPA) at levels commonly found in the general population may cut a woman's chance of getting pregnant if she is undergoing fertility treatment, a study from Harvard University finds. Those with higher BPA levels were less likely to get pregnant than women with lower levels. The link was stronger in women having more intense fertility treatments. The pregnancies failed because the embryos did not attach to the uterus.

While animal studies show similar results, this is the first time researchers report a link in people. BPA is widely used in some plastics, most food can linings and certain receipt paper.

 

Context

The Centers for Disease Control and Prevention estimate that about 6.1 million women in the United States have trouble getting or staying pregnant. This is partly because they are having babies at an older age.

One type of fertility problem is when the embryo(s) fails to implant in the uterus. This accounts for up to 75 percent of preclinical pregnancy loss – an early loss that ends before a woman's next menstrual period. Successful implantation requires proper hormone function and response.

Studies suggest that continuous exposure to endocrine-disrupting chemicals like bisphenol A (BPA) lead to fertility problems such as failed embryo implantation. Endocrine disruptors are a group of chemicals that can behave like or block hormones, including the reproductive hormones involved in pregnancy.

Bisphenol A is widely used in the manufacture of polycarbonate plastics and epoxy resins. It is in many consumer products, including the lining of food and beverage cans, plastic food containers, dental sealants, cigarette filters, water supply pipes and paper receipts. Thus, exposure in the general population is widespread.

Exposure to BPA is mainly through contaminated food. It can also be breathed in or absorbed in the skin.

In animals, BPA exposure at levels measured in the general population is linked to reproductive problems, including failed implantation, reduced litter size and lower percentage of females having pups. In humans, limited studies indicate that BPA exposure is associated with reproductive problems. BPA exposure in women undergoing in vitro fertilization (IVF) is related to lower quality and number of eggs retrieved during treatment and the level of hormones essential to get pregnant.

Studying the effects of endocrine disruptors, like BPA, on reproductive health can be a challenge in couples trying to get pregnant naturally. IVF allows researchers to have a look into the earliest stages of pregnancy usually not observable in couples conceiving naturally. Implantation failure, for example, happens before a woman knows she’s pregnant.

For many couples, IVF is the only way to get pregnant. During IVF, a woman takes fertility drugs to stimulate the ovaries to produce more eggs. The process is then monitored via blood tests and an ultrasound exam. To trigger ovulation, a woman is given hormones before collecting her eggs. Once retrieved from the woman’s ovaries, the eggs are fertilized with sperm in a laboratory dish in hopes that one or more will grow into a viable embryo. Lastly, the embryo – fertilized egg(s) – is transferred to the woman’s uterus.

What did they do?

Researchers followed 137 women seeking fertility treatment at Massachusetts General Hospital Fertility Center. They examined the relationship between BPA exposure and pregnancy success among women undergoing IVF treatment.

Women were of childbearing age (18-45 years), used their own eggs in the IVF procedure and most were Caucasian and non-smokers. They were followed through each IVF cycle until they delivered their baby or stopped treatment. The participants underwent one of three IVF treatment protocols based on whether they were "poor responders" or "good responders." Women who are “poor responders” require large doses of fertility drugs and end up with fewer eggs.

BPA concentrations in urine samples were measured at each fertility treatment. The researchers confirmed pregnancies – defined as successful embryo implantation – by measuring the levels in blood samples of a hormone produced during pregnancy – ß-human chorionic gonadotropin hormone (ß-HCG). The hormone is found in blood and urine of pregnant women as early as 10 days after conception.

Medical history, lifestyle factors, occupation and other personal information were collected in a nurse-administered questionnaire and/or in an in-depth take-home questionnaire. 

Researchers categorized women into one of four exposure groups based on the BPA levels in their urine: 1.69 micrograms per liter (μg/L) or lower, 1.70-2.33 μg/L, 2.34-3.79 μg/L and 3.80 μg/L or higher. They compared the chances of getting pregnant in women in the highest exposure groups (1.70 μg/L and higher) to women in the lowest exposure group (1.69 μg/L or lower).

In their analysis, they considered several factors that could affect the association between BPA exposure and implantation failure, including women’s age, day of embryo transfer and specific IVF protocol treatment followed.

What did they find?

Regardless of the factors considered, the results show a clear trend of increasing implantation failure with higher BPA levels. These effects were observed in women with BPA levels lower than those in women of childbearing age in the general U.S. population.

Average levels of BPA measured in the women's urine – 1.53 μg/L – were comparable to those reported in women from the general U.S. population – 1.97 μg/L.

Without taking into account women’s age, day of embryo transfer and IVF protocol followed, the chances of getting pregnant decreased with increasing exposure levels of BPA. Women in the highest exposure group had half the odds of getting pregnant than women with the lowest levels.

Findings were similar after controlling for women’s age, day of embryo transfer, and IVF protocol followed. The relationship was not as strong in women in the highest exposure group.

Researchers also observed stronger associations between BPA and failed pregnancies in women who were poor responders. Those with higher levels of BPA were less likely to become pregnant. Women who were poor responders were generally older and more likely to have past IVF treatment cycle failures. They also had reduced number of eggs, lower average number of eggs retrieved and diminished ovarian response to stimulation.

What does it mean?

This is the first study to find an association between failed egg implantation and BPA exposure in women undergoing IVF treatment.

This finding is important because it provides the first human data on the association between implantation failure in women seeking IVF treatment and BPA exposure at levels observed in women of childbearing age in the general population. Results suggest that as BPA levels increase so do the number of failed pregnancies in women undergoing fertility treatment.

These findings confirm in people what has been observed in animal studies and support previous studies that link BPA to fertility problems in humans. Prior studies in humans report that BPA exposure is associated with recurrent miscarriages, quality and number of eggs retrieved during IVF treatment and peak hormone levels essential for a successful pregnancy.

Additionally, findings support earlier studies that suggest women seeking IVF treatment minimize their exposure to BPA (Fujimoto et al. 2011; Mol-Lin et al. 2010).

The results may not be applicable to women trying to conceive naturally. According to the authors, it is possible that women undergoing fertility treatment are more sensitive to BPA exposure due to different factors “including their underlying infertility, the in vitro conditions of early embryonic development or the ovarian hyperstimulation protocols.”

Nonetheless, because 10-15 percent of the population in the United States and developed countries are infertile, the results are still relevant to a large subset of the general population. 

Resources

Fujimoto, VY, D Kim D, FS vom Saal, JD Lamb, JA Taylor and MS, Bloom. 2011. Serum unconjugated bisphenol A concentrations in women may adversely influence oocyte quality during in vitro fertilization. Fertility and Steriityl 95(5):1816-1819.

Infertility FAQs. Centers for Disease Control and Prevention.

Macklon, NS, JP Geraedts and BC Fauser. 2002. Conception to ongoing pregnancy: the 'black box' of early pregnancy loss. Human Reproduction Update 8(4):333-343.

Mok-Lin, E, S Ehrlich, PL Williams, J Petrozza, DL Wright AM Calafat, X Ye and R Hauser. 2010. Urinary bisphenol A concentrations and ovarian response among women undergoing IVF. International Journal of Andrology 33(2):385-393.

Sugiura-Ogasawara, M, Y Ozaki, S Sonta, T Makino and K Suzumori. 2005. Exposure to bisphenol A is associated with recurrent miscarriage. Human Reproduction 20(8):2325-2329.

Takai, Y, O Tsutsumi, Y Ikezuki, H Hiroi, Y Osuga, M Momoeda, T Yanoa and Y Taketani.. 2000. Estrogen receptormediated effects of a xenoestrogen, bisphenol A, on preimplantation mouse embryos. Biochemical and Biophysical Research Communication 270(3):918-921.

Xiao, S, D Honglu, MA Smith, X Song and X Ye. 2011. Preimplantation exposure to bisphenol A (BPA) affects embryo transport, preimplantation embryo development, and uterine receptivity in mice. Reproductive Toxicology 32(4):434–441.

 

 

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