Association between serum folate and vitamin B-12 and outcomes of assisted reproductive technologies

Abstract

Background: Preconceptional folate and vitamin B-12 have been linked to beneficial reproductive outcomes in both natural pregnancies and those after assisted reproductive technology (ART) treatment.

Objective: The objective of the study was to evaluate the associations of serum folate and vitamin B-12 with ART outcomes.

Design: This analysis included a random sample of 100 women (154 ART cycles) participating in a prospective cohort study [Environment and Reproductive Health (EARTH)] at the Massachusetts General Hospital Fertility Center (2007-2013). Serum folate and vitamin B-12 were measured in blood samples collected between days 3 and 9 of treatment. Generalized estimating equations with adjustment for age, BMI, and race were used to evaluate the association of serum folate and vitamin B-12 with ART outcomes.

Results: Women in the highest quartile of serum folate (>26.3 ng/mL) had 1.62 (95% CI: 0.99, 2.65) times the probability of live birth compared with women in the lowest quartile (<16.6 ng/mL). Women in the highest quartile of serum vitamin B-12 (>701 pg/mL) had 2.04 (95% CI: 1.14, 3.62) times the probability of live birth compared with women in the lowest quartile (<439 pg/mL). Suggestive evidence of an interaction was observed; women with serum folate and vitamin B-12 concentrations greater than the median had 1.92 (95% CI: 1.12, 3.29) times the probability of live birth compared with women with folate and vitamin B-12 concentrations less than or equal to the median. This translated into an adjusted difference in live birth rates of 26% (95% CI: 10%, 48%; P = 0.02).

Conclusion: Higher serum concentrations of folate and vitamin B-12 before ART treatment were associated with higher live birth rates among a population exposed to folic acid fortification. This trial was registered at clinicaltrials.gov as NCT00011713.

Keywords: assisted reproduction; folate; in vitro fertilization; infertility; pregnancy; vitamin B-12.

© 2015 American Society for Nutrition.

Figures

FIGURE 1

Distribution of serum folate (A) and vitamin B-12 (B) concentrations in 100 women from the Environment and Reproductive Health Study (2007–2013).

FIGURE 2

Interaction between serum folate and vitamin B-12 concentrations and live birth after assisted reproduction in 100 women (154 initiated cycles) from the Environment and Reproductive Health Study (2007–2013). The analyses were conducted by using generalized estimating equations with a binomial distribution and log link function with adjustment for age (continuous), BMI (continuous), and race (white, other). P-interaction = 0.58. *P < 0.05 compared with the reference category of women with both serum folate and vitamin B-12 concentrations below the median.