Lathi RB, Liebert CA, Brookfield KF, et al. Conjugated bisphenol A in maternal serum in relation to miscarriage risk. Fertil Steril. 2014;102(1):123-128.
Retrospective cohort of prospectively collected serum samples.
In all, 115 pregnant women who sought treatment for infertility or recurrent pregnancy loss at the Stanford Fertility and Reproductive Medicine Clinic, Palo Alto, California, were studied; 47 had live births, and 68 experienced a first trimester miscarriage. The women were similar in terms of age, body mass index, day 3 follicle-stimulating hormone level, and smoking status. In order to evaluate unexplained miscarriage rates, women with abnormal karyotype, uterine anomalies, thrombophilia, autoimmune disorders, and uncontrolled diabetes were excluded.
Stored serum samples from 4 to 5 weeks gestation were analyzed for conjugated serum bisphenol A (BPA) concentration
Primary Outcome Measures
Live-birth rate, first trimester miscarriage rate, and karyotype of embryo if miscarried.
Of the 115 women included in the study, 47 had live births and 68 experienced a miscarriage (46 aneuploid and 22 euploid). Median conjugated BPA levels were higher in women who miscarried (0.101 ng/mL) compared to women who had a live birth (0.075 ng/mL, P=0.014). Women who had a serum BPA level in the highest quartile had an 83% higher risk of experiencing a first trimester miscarriage than women with a serum BPA level in the lowest quartile.
In this study, maternal conjugated BPA was associated with a higher risk of a first trimester miscarriage. BPA is an endocrine-disrupting chemical that can interfere with the production, metabolism, and action of hormones involved in reproduction and embryo development.1 BPA is found in the lining of metal food cans, thermal receipt paper, plastic food and beverage containers, dental sealants, and medical devices. The National Health and Nutrition Examination Survey collected urine samples from 2517 individuals over the age of 6 years old and found detectable levels of BPA in 93% of samples, demonstrating widespread exposure to BPA.2 In addition, BPA exposure has been linked with endometriosis, infertility, and polycystic ovarian syndrome.3,4 Previous animal studies have shown that low-dose BPA exposure can increase meiotic errors in maturing mice ovarian follicles,5 as well as altered endometrial progesterone receptor expression in nonhuman primates.6
In previous studies assessing serum BPA levels, concern was raised that the blood collection process itself caused BPA contamination; however, this study addresses the concern of contamination by measuring conjugated BPA that had undergone glucoronidation in the human liver. Because previous animal studies have shown that periconception BPA exposure has a negative effect on endometrial health and follicular development, another strength of this study is that it measured serum BPA levels during early pregnancy to determine the effects of periimplantation BPA exposure on miscarriage rates.
Future studies should evaluate the relationship of embryo quality and miscarriage rate in relation to male BPA exposure. Naturopathic physicians who are offering preconception care and treating patients with recurrent pregnancy loss should consider the importance of avoiding environmental exposures like BPA and other endocrine disruptors in improving embryo health and reducing the chance of miscarriage.
- Vandenberg LN, Colborn T, Hayes TB, et al. Hormones and endocrine disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocr Rev. 2012;33(3):378-455.
- National Institute of Environmental Health Sciences. National Toxicology Program. Bisphenol A (BPA). Available at: http://www.niehs.nih.gov/health/assets/docs_a_e/bisphenol_a_bpa_508.pdf. Accessed September 8, 2014.
- Maffini MV, Rubin BS, Sonnenschein C, Soto AM. Endocrine disruptors and reproductive health: the case of bisphenol-A. Mol Cell Endocrinol. 2006 Jul 25;254-255:179-186.
- Rochester JR. Bisphenol A and human health: a review of the literature. Reprod Toxicol. 2013 Dec;42:132-155.
- Susiarojo M, Hassold TJ, Freeman E, Hunt PA. Bisphenol A exposure in utero disrupts early oogenesis in the mouse. PLoS Genet. 2007;3(1):e5.
- Aldad TS, Rahmani N, Leranth C, Taylor HS. Bisphenol-A exposure alters endometrial progesterone receptor expression in nonhuman primate. Fertil Steril. 2011;96(1):175-179.