Serum omega-3 fatty acids and treatment outcomes among women undergoing assisted reproduction

Abstract

Study question: Are serum polyunsaturated fatty acids (PUFA) concentrations, including omega-3 (ω3-PUFA) and omega-6 (ω6-PUFA), related to ART outcomes?

Summary answer: Serum levels of long-chain ω3-PUFA were positively associated with probability of live birth among women undergoing ART.

What is known already: Intake of ω3-PUFA improves oocyte and embryo quality in animal and human studies. However, a recent cohort study found no relation between circulating ω3-PUFA levels and pregnancy rates after ART.

Study design size, and duration: This analysis included a random sample of 100 women from a prospective cohort study (EARTH) at the Massachusetts General Hospital Fertility Center who underwent 136 ART cycles within one year of blood collection.

Participants/materials, setting, methods: Serum fatty acids (expressed as percentage of total fatty acids) were measured by gas chromatography in samples taken between Days 3 and 9 of a stimulated cycle. Primary outcomes included the probability of implantation, clinical pregnancy and live birth per initiated cycle. Cluster-weighted generalized estimating equation (GEE) models were used to analyze the association of total and specific PUFAs with ART outcomes adjusting for age, body mass index, smoking status, physical activity, use of multivitamins and history of live birth.

Main results and role of chance: The median [25th, 75th percentile] serum level of ω3-PUFA was 4.7% [3.8%, 5.8%] of total fatty acids. Higher levels of serum long-chain ω3-PUFA were associated with higher probability of clinical pregnancy and live birth. Specifically, after multivariable adjustment, the probability of clinical pregnancy and live birth increased by 8% (4%, 11%) and 8% (95% CI: 1%, 16%), respectively, for every 1% increase in serum long-chain ω3-PUFA levels. Intake of long-chain ω3-PUFA was also associated with a higher probability of life birth in these women, with RR of 2.37 (95% CI: 1.02, 5.51) when replacing 1% energy of long-chain ω3-PUFA for 1% energy of saturated fatty acids. Serum ω6-PUFA, ratios of ω6 and ω3-PUFA, and total PUFA were not associated with ART outcomes.

Limitations reasons for caution: The generalizability of the findings to populations not undergoing infertility treatment may be limited. The use of a single measurement of serum fatty acids to characterize exposure may lead to potential misclassification during follow up.

Wider implications of the findings: Serum ω3-PUFA are considered biomarkers of dietary intake. The association of higher serum long chain ω3-PUFA levels with improved ART outcomes suggests that increased intake of these fats be may be beneficial for women undergoing infertility treatment with ART.

Study funding/competing interests: NIH grants R01-ES009718 from the National Institute of Environmental Health Sciences, P30-DK046200 and T32-DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases, and L50-HD085359 from the National Institute of Child Health and Human Development, and the Early Life Nutrition Fund from Danone Nutricia US. Dr Rueda is involved in a patent 9,295,662, methods for enhancing, improving, or increasing fertility or reproductive function (http://patents.com/us-9295662.html). This patent, however, does not lead to financial gain for Dr Rueda, or for Massachusetts General Hospital. Dr Rueda does not own any part of the company nor does he have any equity in any fertility related company. As Dr Rueda is not a physician, he does not evaluate patients or prescribe medications. All other coauthors have no conflicts of interest to declare.

Keywords: ART; clinical pregnancy; live birth; omega-3 fatty acids; polyunsaturated fatty acids.

© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Figures

Figure 1

Major pathways of polyunsaturated fatty acids.

Figure 2

Major food sources of long-chain ω-3 fatty acids in the EARTH participants. Others included cod liver oil supplement, breaded fish cakes or fish sticks, muffin and cakes. Examples of dark meat fish are tuna, mackerel, salmon, sardines, bluefish, swordfish, etc.

Figure 3

Risk ratios (RR) of clinical outcomes following ART by substituting long-chain ω-3 fatty acids for different sources of macronutrients among 168 women (297 cycles). Models were adjusted for age, BMI, smoking status, moderate-to-vigorous physical activity, use of multivitamins, history of live birth, total calories, protein intake, dietary patterns and other types of fatty acids. The number in the figure represents the risk ratio (RR) for each of the clinical outcome substituting 1% of calories from long-chain ω-3 fatty acids for 1% of calories from different sources of macronutrients. SFA, saturated fatty acid intake; MUFA, monounsaturated fatty acid intake; PUFA, polyunsaturated fatty acid intake; RR, risk ratio.