Authors
Sugiura-Ogasawara M, Ozaki Y, Sonta S, Makino T, Suzumori K.

Title
Exposure to bisphenol A is associated with recurrent miscarriage

Source
Human Reproduction 2005; 20(8):2325-9

Summary
Bisphenol A (BPA) is an endocrine disrupter with estrogenic activity. Materials such as polycarbonate plastics, epoxy resins, dental sealants and many others in our environment contain BPA, resulting in human exposure worldwide. Animal experiments indicated alterations in post-natal development and sexual maturity in the off-spring of pregnant mice exposed to BPA. Moreover, daily administration of BPA in mice resulted in meiotic aneuploidy, which was identified as one of the reasons for recurrent miscarriages. However, human evidence was controversial.

In this study, the relationship between BPA exposure in pregnant women and recurrent miscarriage was studied. In addition, the association between serum BPA levels and certain endocrine and immunological abnormalities was also examined. The case group constituted of 45 patients with a history of three or more consecutive first-trimester miscarriages, seen at Nagoya City University Hospital between August 2001 and December 2002. Fasting blood samples were obtained. A series of tests were performed for all the patients, viz., hystrerosalpingography, immunological tests for antinuclear antibodies (ANAs), antiphospholipid antibodies (aPLs), natural killer cell activity, and blood tests for diabetes mellitus, hypothyroidism and hyperprolactinaemia. Those with a uterine anomaly or chromosomal abnormality in either partner were excluded. A total of 32 healthy hospital staff, including doctors, nurses and secretaries who were non-pregnant, with no history of live birth, infertility or miscarriage constituted the control group. The subjects were followed prospectively to assess the pregnancy outcome and karyotype of abortuses.

Serum BPA levels of case and control women were compared. In addition, serum BPA levels were also compared between patients with successful pregnancies and patients with subsequent miscarriage with and without an abnormal embryonal karyotype and with and without hypothyroidism, aPLs, ANAs, and hyperprolactinaemia. Correlations with endocrine and immunological characteristics were also examined. The mean ± standard deviation (SD) serum BPA values of cases (2.59 ± 5.23) was found to be significantly higher than the control women (0.77 ± 0.38). Although, higher levels of BPA were found in patients who miscarried, they are not significantly different from the levels in patients who had successful pregnancies. Four abnormal karyotypes were observed among the 13 abortuses analyzed. The individual BPA levels of ANA-positive patients were significantly higher compared to the levels in ANA-negative patients. However, no such association was observed between patients with and without hypothyroidism, hyperprolactinaemia (luteal phase defect), and presence of aPLs.

In summary, this study indicated that high exposure to BPA may be associated with recurrent miscarriage, particularly in ANA positive patients. However, it should be noted that high level of BPA in the serum is not the lone predictor of recurrent miscarriage. Chromosomal abnormalities of the conceptus, were believed to cause 40-70% of the sporadic spontaneous abortions, aneuploidy being particularly important. Scientific evidence indicates the presence of abnormal karyotype of conceptus in approximately 10-50% of recurrent miscarriage cases. However, the cause of recurrent miscarriages in over 50% of the cases is unclear. Age of women also plays key role in miscarriage and aneuploidy rate. Aneploidy rate was found to decrease with the number of abortions. Considering above information, the authors of this study expected that 18% of the recurrent abortions were due to embryonal chromosomal abnormalities and that high serum BPA levels might be the culprit for these cases. Small sample size is a limitation for this study. Overall, this study indicated an association between BPA exposure and recurrent miscarriage in humans.