Secondary Logo

Institutional members access full text with Ovid®

Intake of Antioxidants in Relation to Infertility Treatment Outcomes with Assisted Reproductive Technologies

Li, Ming-Chieha,b; Nassan, Feiby L.a,c; Chiu, Yu-Hana; Mínguez-Alarcón, Lidiac; Williams, Paige L.d,e; Souter, Irenef; Hauser, Russc,d,f; Chavarro, Jorge E.a,d,g for the EARTH Study Team

doi: 10.1097/EDE.0000000000000976
Perinatal Epidemiology

Background: Randomized trials of supplementation with antioxidant mixtures during infertility treatment show no benefit on pregnancy or live birth rate. However, the roles of individual antioxidants are poorly understood. We examined the association of baseline intake of vitamins A, C, E, and carotenoids with outcomes of assisted reproductive technologies (ARTs).

Methods: We followed 349 women undergoing a total of 588 ART cycles for infertility treatment at the Massachusetts General Hospital. We assessed antioxidant intakes from food and supplements before treatment using a validated food frequency questionnaire. We used generalized linear mixed models to account for multiple ART cycles per woman while adjusting for confounding.

Results: Mean (SD) age and body mass index were 35.1 years (4.0 years) and 24.1 kg/m2 (4.3 kg/m2), respectively. Total intake of vitamins A, C, and E was not associated with the probability of live birth. Women in the highest intake category of β-carotene from foods had a lower probability of live birth than women in the lowest intake quartile (50% vs. 22%; P trend = 0.03); for lutein and zeaxanthin, the probability for the highest intake group was 44% vs. 28% for the lowest. Intake of β-carotene from supplements and intakes of retinol and all other carotenoids were unrelated to live birth rates.

Conclusions: We found unexpected inverse associations of β-carotene intake from foods and of lutein and zeaxanthin intake with live birth rates. Within the observed intake ranges, total consumption of vitamins A, C, and E before starting infertility treatment with ART was not associated with live birth rates.

From the aDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA

bDepartment of Public Health, China Medical University College of Public Health, Taichung, Taiwan

cDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA

dDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA

eDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA

fDepartment of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Massachusetts General Hospital Fertility Center, Harvard Medical School, Boston, MA

gChanning Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA.

Submitted June 7, 2018; accepted January 23, 2019.

The EARTH Study Team are Charles Bormann, PhD HCLD, Massachusetts General Hospital; Courtney Carignan, PhD, Yu-Han Chiu, MD, MPH, ScD, Georgios Christou, MD, Ramace Dadd, BA, Jennifer B. Ford, RN, BSN, Tamarra James-Todd, MPH, PhD, Myra G. Keller, RNC, BSN, Carmen Messerlian, PhD, Lidia Mínguez-Alarcón, PhD, Feiby Nassan, ScD, and Paige Williams, MS, PhD, Harvard T.H. Chan School of Public Health; Jorge Chavarro, MD, ScM, ScD, and Audrey J. Gaskins, ScD, Harvard T.H. Chan School of Public Health and Brigham and Women’s Hospital, Harvard Medical School; Russ Hauser, MD, ScD, MPH, Harvard T.H. Chan School of Public Health and Massachusetts General Hospital, Harvard Medical School; John Petrozza, MD, Mary Sabatini, MD, PhD, Jan Shifren, MD, Irene Souter, MD, Cigdem Tanrikut, MD, and Thomas L. Toth, MD, Massachusetts General Hospital and Harvard Medical School.

Supported by the National Institutes of Health (P30ES000002, R01ES009718, R01ES022955, and P30DK046200). M.-C.L. was supported by the Ministry of Science and Technology, Taiwan (MOST 106-2917-I-564-066).

Disclosure: The authors report no conflicts of interest.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article ( This content is not peer-reviewed or copy-edited; it is the sole responsibility of the authors.

Availability of data and code for replication: All data used and computing code developed for the analyses described in this article are available upon request, subject to the access requirements of the institutions.

Correspondence: Jorge E. Chavarro, Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115. E-mail:

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.