Dietary folate and reproductive success among women undergoing assisted reproduction

Abstract

Objective: To prospectively evaluate the associations of folate with assisted reproductive technology outcomes within a population in the United States.

Methods: This analysis included women (n=232) in a prospective cohort study at the Massachusetts General Hospital Fertility Center. Diet was assessed before assisted reproductive technology treatment using a validated food frequency questionnaire. Intermediate and clinical endpoints of assisted reproductive technology were abstracted from medical records. Generalized linear mixed models with random intercepts to account for multiple cycles per woman were used to evaluate the association of folate intake with assisted reproductive technology outcomes adjusting for calorie intake, age, body mass index, race, smoking status, infertility diagnosis, and protocol type.

Results: Among the 232 women (median age 35.2 years, median folate intake 1,778 micrograms/day), higher folate intake was associated with higher rates of implantation, clinical pregnancy, and live birth. The adjusted percentage (95% confidence interval [CI]) of initiated assisted reproductive technology cycles resulting in a live birth for women in increasing quartiles of folate intake were 30% (95% CI 21-42%), 47% (95% CI 35-59%), 42% (95% CI 30-35%) and 56% (95% CI 43-67%) (P for trend=0.01). Live birth rates were 20% (95% CI 8-31%) higher among women in the highest quartile of supplemental folate intake (more than 800 micrograms/day) than among women in the lowest quartile (less than 400 micrograms/day). Higher supplemental folate intake was associated with higher fertilization rates and lower cycle failure rates before embryo transfer (P for trend=0.03 and 0.02).

Conclusion: Higher intake of supplemental folate was associated with higher live birth rates after assisted reproductive technology treatment.

Level of evidence: : II.

Figure 1

Overview of assisted reproductive technology outcomes of 232 women (353 cycles) in the Environment and Reproductive Health Study.

Figure 2

Associations between folate intake and live birth rates in 232 women (353 initiated cycles) from the Environment and Reproductive Health Study. Shown are the associations between total folate (in dietary folate equivalents) (A) and supplemental folate (B) and live birth rate per initiated cycle after assisted reproductive technology. All analyses were run using a generalized linear mixed model with random intercepts, binomial distribution, and logit link function. The solid line represents the adjusted mean live birth rate by level of folate intake and the dotted lines are the upper and lower 95% confidence intervals for these adjusted means. Adjusted means presented for average total calorie intake (1797 kcals/day), age (35 years), body mass index (24.3 kg/m²), race (white), smoking status (never smoker), infertility diagnosis (female factor), and protocol type (luteal phase agonist).