Pre-conceptional supplementation with folic acid is recognized as essential for the prevention of neural tube defects. However, the reproductive effects of folic acid may extend well beyond this well-recognized effect and may have an important role in improving fertility and survival of the conceptus and fetus.
Materials and methods
We evaluated the association between pre-conceptional intake of folic acid from foods and supplements in relation to fertility-related outcomes in two prospective cohort studies: the Nurses’ Health Study II and the EARTH Study. In the Nurses’ Health Study II we evaluated the association between pre-conceptional folic acid intake and risks of ovulatory infertility and pregnancy loss. In the EARTH Study, a prospective cohort of couples undergoing infertility treatment, we evaluated the association between pre-treatment folic acid intake and treatment outcomes focusing on live birth rates.
Folic acid intake was associated with lower risk of ovulatory disorder infertility (Chavarro et al. Fertil Steril 2008) and clinical pregnancy loss (Gaskins et al. Obstet Gynecol 2014a) and was positively related to live birth rates among women undergoing assisted reproduction (Gaskins et al. Obstet Gynecol 2014b). Specifically, compared to women in the lowest quartile of folic acid intake, women in the highest quartile of intake had a 39% lower risk of ovulatory disorder infertility, 20% lower risk of pregnancy loss (spontaneous abortion and stillbirth) and 20% higher live birth rate among women undergoing assisted reproduction. The benefit of folic acid was apparent at intakes substantially higher than those currently recommended for the prevention of neural tube defects.
Supplemental folic acid at doses substantially higher than those currently used for the prevention of neural tube defects is associated to better reproductive outcomes among women trying to conceive naturally and those undergoing assisted reproduction. These results should be further evaluated in randomized controlled trials.