Folate intake and ovarian reserve among women attending a fertility center

Abstract

Objective: To examine the association between dietary folate intake and antral follicle count (AFC) among women seeing treatment for infertility.

Design: Cohort study.

Setting: Academic fertility center.

Patients: A total of 552 women attending the Massachusetts General Hospital Fertility Center (2007-2019) who participated in the Environment and Reproductive Health Study.

Interventions: None. Folate intake was measured with a validated food frequency questionnaire at study entry. Multivariable Poisson regression models with robust standard errors were used to estimate the association of folate intake with AFC adjusting for calorie intake, age, body mass index, physical activity, education, smoking status, year of AFC, and intakes of vitamin B12, iron, and vitamin D. Nonlinearity was assessed with restricted cubic splines.

Main outcome measure: AFC as measured by transvaginal ultrasonography as part of routine care.

Results: Among the 552 women (median age, 35.0 years; median folate intake, 1,005 μg/d), total and supplemental folate intake had a significant nonlinear relationship with AFC. There was a positive linear association with AFC up to approximately 1,200 μg/d for total folate intake and up to 800 μg/d for supplemental folate intake; however, there was no additional benefit of higher folate intakes. The magnitude of the association was modest; for example, the predicted adjusted difference in AFC between a woman consuming 400 vs. 800 μg/d of supplemental folate was approximately 1.5 follicles.

Conclusion: Higher intake of folate, particularly from supplements, was associated with modestly higher ovarian reserve as measured by AFC among women attending a fertility center.

Clinical trial registration number: This trial was registered at clinicaltrials.gov as NCT00011713.

Keywords: Antral follicle count; female fertility; folate; folic acid; ovarian reserve.

Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.

Associations between total folate intake (panel A), supplemental folate intake (panel B), and food folate (panel C) and antral follicle count fit using restricted cubic splines among 552 women in the EARTH Study. The solid line represents the adjusted mean AFC and the shaded grey area represents the 95% confidence interval. The models are adjusted for total calorie intake, age, BMI, physical activity, education level, smoking status, year of AFC (antral follicle count), vitamin B12, iron, and vitamin D intake. The p-value for non-linearity was 0.05 for total folate, 0.02 for supplemental folate, and 0.23 for food folate. For all figures, the x-axis extends from the 5th to 95th percentile of the intake distribution for that nutrient.

Figure 1.

Associations between total folate intake (panel A), supplemental folate intake (panel B), and food folate (panel C) and antral follicle count fit using restricted cubic splines among 552 women in the EARTH Study. The solid line represents the adjusted mean AFC and the shaded grey area represents the 95% confidence interval. The models are adjusted for total calorie intake, age, BMI, physical activity, education level, smoking status, year of AFC (antral follicle count), vitamin B12, iron, and vitamin D intake. The p-value for non-linearity was 0.05 for total folate, 0.02 for supplemental folate, and 0.23 for food folate. For all figures, the x-axis extends from the 5th to 95th percentile of the intake distribution for that nutrient.

Figure 1.

Associations between total folate intake (panel A), supplemental folate intake (panel B), and food folate (panel C) and antral follicle count fit using restricted cubic splines among 552 women in the EARTH Study. The solid line represents the adjusted mean AFC and the shaded grey area represents the 95% confidence interval. The models are adjusted for total calorie intake, age, BMI, physical activity, education level, smoking status, year of AFC (antral follicle count), vitamin B12, iron, and vitamin D intake. The p-value for non-linearity was 0.05 for total folate, 0.02 for supplemental folate, and 0.23 for food folate. For all figures, the x-axis extends from the 5th to 95th percentile of the intake distribution for that nutrient.