Thursday, October 3, 2013

BPA and In Vitro Fertilization: Making Things Hard For People Already Struggling to Conceive

There is a whole host of research out there examining the effects of Bisphenol A (BPA) on reproduction both in vitro (a.k.a. in the lab) and in vivo in various species of animal.  Though one can often translates the effects of in vitro studies and in vivo studies on animals to how things might happen in humans, however, this is not always the case.  Therefore, there is a need to provide evidence in the human body prior to making sweeping judgments on the results based on effects seen in other animals or in the test tube.

In the mouse model, studies have shown that exposure to BPA at doses known to be present in the environment increases oocyte aneuploidy, which may result in miscarriage or severe birth defects.  Further studies elaborate on the mechanism behind this error in chromosome distribution in egg cells showing that BPA contributes to increased aneuploidy by disrupting meiotic spindle formation, as well as centrosome behavior and chromosome alignment and subsequent division.  Adding to the list of negative reproductive effects in animal models, BPA has been shown to inhibit the production of the natural hormone, estradiol, as well as negatively impacting fertility in general.

What about human studies?

Preliminary studies looking at the effects of BPA in humans, specifically in the area of in vitro fertilization (IVF), have shown that there may be significant negative relationships between BPA levels in urine and decreases estradiol and numbers of eggs retrieved at the finale of the IVF retrieval process.  There have been very few studies directly examining the effects of BPA on women undergoing the IVF process, in particular the associations between BPA and early reproductive outcomes, oocyte quality, and early embryonic growth (i.e. cleavage) rates.

Just last year, a group at Massachusetts General Hospital in Boston, MA,  a teaching hospital affiliated with Harvard University, set out to determine how BPA influenced the IVF process, in particular effects on the quality of the egg and developing embryo, as well as fertilization rates and cleavage rate of the developing blastocyst. 


The MGH team looked at a group of women undergoing IVF procedures using their own eggs (i.e. not donor eggs) and analyzed the levels of BPA present in their urine.  Additionally, they were asked general questions about demographics, medical history, lifestyle, and finally occupational history.  On the day of egg retrieval, the number of MII oocytes as well as the percentage of mature oocytes from all of the oocytes collected during the retrieval (i.e. maturation rate) were measured or calculated.  The fertilization rates of these mature oocytes were also calculated.

After fertilization was complete, the quality of embryos on Day 5 of development was determined by counting the number of cells present in the developing blastocysts.   

BPA & IVF = A Match Made in Hell?

What the team at MGH found in these women undergoing IVF treatment for their infertility was that BPA levels in urine resulted in a fewer number of oocytes retrieved per IVF cycle, as well as a decreased level of estradiol on the day of HCG (human chorionic gonadotropin) administration when estradiol levels should be at their peak.  Earlier studies in IVF research have shown that serum estradiol levels and the number of oocytes retrieved per IVF cycle are strong predictors of IVF success in humans. 

Specifically, the MGH researchers found that there was a significant drop in the numbers of mature oocytes as well as the number of normal oocytes successfully fertilized during the IVF process, which were both correlated with BPA levels in the urine.  In terms of embryo quality, no significant associations were noted in terms of embryo quality and BPA levels in urine, however, the team at MGH stressed that this result may be bias due to the nature of their experimental design.  This question remains to be answered and would be an important focus for future research.

Overall, the results of this trial were disconcerting for those undergoing IVF treatment.  If you were exposed to a higher level of BPA, you may have a much harder time getting pregnant not only by natural methods, but also by IVF intervention.  With increased BPA levels in the body, the sheer number of mature eggs ready for fertilization is lower than it would be normally, and estradiol, a key hormone during the maturation and fertilization processes, is also significantly lower in concentration due to this BPA exposure.

Could it be that BPA may be both causing infertility as well as preventing the current IVF fertility treatments from succeeding?  Certainly more needs to be examined here, but from this study it seems to be clear that higher BPA levels present in the urine of women undergoing IVF treatment are at a significant disadvantage to successfully conceiving than their counterparts that have not been exposed to the endocrine disrupting BPA.

Source: Ehrlich, S., Williams, P.L., Missmer, S.A., Flaws, J.A., Ye, X., Calafat, A.M., Petrozza, J.C., Wright, D., and Hauser, R. 2012. Urinary Bisphenol A concentrations and early reproductive health outcomes among women undergoing IVF. Human Reproduction 27(12):3583-3592.

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