Serum omega-3 and omega-6 fatty acid concentrations and natural fertility.

study questionAre serum omega-3 and omega-6 essential fatty acid concentrations associated with the probability of conceiving? SUMMARY ANSWER: There is no strong association between serum concentrations of omega-3 and omega-6 fatty acids and the probability of conceiving naturally. WHAT IS KNOWN ALREADY: Omega-3 and omega-6 fatty acid serum concentrations have been shown to play an important role in reproduction in animal models, while conflicting results have been reported in human studies of infertile women. It is unknown to what extent omega fatty acid serum concentrations impact natural fertility. STUDY DESIGN, SIZE, DURATION: A nested, case-control study was conducted consisting of 200 participants [fertile: conceived within 3 cycles of attempt (n = 50), subfertile: conceived within 4 and 12 cycles of attempt (n = 100) and infertile: did not conceive within 12 cycles of attempt (n = 50)] randomly selected from the Time to Conceive cohort, a prospective time-to-pregnancy study (2008 to 2015). PARTICIPANTS/MATERIALS, SETTING,

methodsIn the Time to Conceive study, women aged 30-44 years who were trying to conceive for <3 months and had no history of infertility were recruited and followed until the end of their pregnancy or ~1 year of pregnancy attempt. For this study, serum collected early in the woman's pregnancy attempt was analysed for anti-Müllerian hormone (AMH) and omega-3 and omega-6 fatty acid concentrations by liquid chromatography-mass spectrometry. The primary outcome was a positive home pregnancy test. The secondary outcomes were miscarriage and serum AMH level. A discrete-time Cox proportional hazards model was used to estimate the fecundability ratio. The odds ratios for miscarriage were calculated using logistic regression. The association between serum omega fatty acid concentrations and AMH level (natural log transformed) was analysed using Pearson's Correlation. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 200 women provided 1321 cycles for analysis.Mean omega-3, omega-6 and omega-6:omega-3 ratios did not significantly differ between the fertile, subfertile and infertile groups. There were no associations (all fecundability ratios ~1.0) between pregnancy and individual omega-3 fatty acid concentrations, including alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid, or omega-6 fatty acids, including linoleic acid (LA), dihommo-gamma linolenic acid and arachidonic acid. There was no significant association between any individual omega fatty acid serum concentration and the age-adjusted odds of miscarriage. No association was found between any serum omega fatty acid concentration and AMH. LIMITATIONS, REASONS FOR CAUTION: This study is limited by the sample size. Omega-3 and omega-6 fatty acid concentrations were derived from serum provided at a single timepoint in the first cycle of enrollment. Serum concentrations may therefore not be representative of all critical timepoints in the menstrual cycle or throughout their attempts to conceive. Additionally, women enrolled in this study were 30 years of age and older, and therefore the findings may not apply to younger women. WIDER IMPLICATIONS OF THE

findingsThese data would suggest that omega-3 and omega-6 serum levels are not associated with natural fertility or risk of miscarriage. However, due to the above-mentioned limitations, future investigation is still needed to determine whether omega-3 fatty acid supplementation may benefit women planning to conceive naturally. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Division of Reproductive Endocrinology and Infertility at the University of North Carolina at Chapel Hill, by the NIH/NICHD (R21 HD060229-01 and R01 HD067683-01) and, in part, by the Intramural Research Program of the National Institute of Environmental Health Sciences (Z01ES103333). Dr. Jukic received vitamin D supplements for a research study from Theralogix, Inc. The authors have no other conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.