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  1. Abstract STUDY QUESTIONTo what extent is male fatty acid intake associated with fecundability among couples planning pregnancy? SUMMARY ANSWERWe observed weak positive associations of male dietary intakes of total and saturated fatty acids with fecundability; no other fatty acid subtypes were appreciably associated with fecundability. WHAT IS KNOWN ALREADYMale fatty acid intake has been associated with semen quality in previous studies. However, little is known about the extent to which male fatty acid intake is associated with fecundability among couples attempting spontaneous conception. STUDY DESIGN, SIZE, DURATIONWe conducted an internet-based preconception prospective cohort study of 697 couples who enrolled during 2015–2022. During 12 cycles of observation, 53 couples (7.6%) were lost to follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODSParticipants were residents of the USA or Canada, aged 21–45 years, and not using fertility treatment at enrollment. At baseline, male participants completed a food frequency questionnaire from which we estimated intakes of total fat and fatty acid subtypes. We ascertained time to pregnancy using questionnaires completed every 8 weeks by female participants until conception or up to 12 months. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs for the associations of fat intakes with fecundability, adjusting for male and female partner characteristics. We used the multivariate nutrient density method to account for energy intake, allowing for interpretation of results as fat intake replacing carbohydrate intake. We conducted several sensitivity analyses to assess the potential for confounding, selection bias, and reverse causation. MAIN RESULTS AND THE ROLE OF CHANCEAmong 697 couples, we observed 465 pregnancies during 2970 menstrual cycles of follow-up. The cumulative incidence of pregnancy during 12 cycles of follow-up after accounting for censoring was 76%. Intakes of total and saturated fatty acids were weakly, positively associated with fecundability. Fully adjusted FRs for quartiles of total fat intake were 1.32 (95% CI 1.01–1.71), 1.16 (95% CI 0.88–1.51), and 1.43 (95% CI 1.09–1.88) for the second, third, and fourth vs the first quartile, respectively. Fully adjusted FRs for saturated fatty acid intake were 1.21 (95% CI 0.94–1.55), 1.16 (95% CI 0.89–1.51), and 1.23 (95% CI 0.94–1.62) for the second, third, and fourth vs the first quartile, respectively. Intakes of monounsaturated, polyunsaturated, trans-, omega-3, and omega-6 fatty acids were not strongly associated with fecundability. Results were similar after adjustment for the female partner’s intakes of trans- and omega-3 fats. LIMITATIONS, REASONS FOR CAUTIONDietary intakes estimated from the food frequency questionnaire may be subject to non-differential misclassification, which is expected to bias results toward the null in the extreme categories when exposures are modeled as quartiles. There may be residual confounding by unmeasured dietary, lifestyle, or environmental factors. Sample size was limited, especially in subgroup analyses. WIDER IMPLICATIONS OF THE FINDINGSOur results do not support a strong causal effect of male fatty acid intakes on fecundability among couples attempting to conceive spontaneously. The weak positive associations we observed between male dietary fat intakes and fecundability may reflect a combination of causal associations, measurement error, chance, and residual confounding. STUDY FUNDING/COMPETING INTEREST(S)The study was funded by the National Institutes of Health, grant numbers R01HD086742 and R01HD105863. In the last 3 years, PRESTO has received in-kind donations from Swiss Precision Diagnostics (home pregnancy tests) and Kindara.com (fertility app). L.A.W. is a consultant for AbbVie, Inc. M.L.E. is an advisor to Sandstone, Ro, Underdog, Dadi, Hannah, Doveras, and VSeat. The other authors have no competing interests to report. TRIAL REGISTRATION NUMBERN/A. 
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  2. Abstract Some reproductive-aged individuals remain unvaccinated against coronavirus disease 2019 (COVID-19) because of concerns about potential adverse effects on fertility. Using data from an internet-based preconception cohort study, we examined the associations of COVID-19 vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with fertility among couples trying to conceive spontaneously. We enrolled 2,126 self-identified female participants aged 21–45 year residing in the United States or Canada during December 2020–September 2021 and followed them through November 2021. Participants completed questionnaires every 8 weeks on sociodemographics, lifestyle, medical factors, and partner information. We fit proportional probabilities regression models to estimate associations between self-reported COVID-19 vaccination and SARS-CoV-2 infection in both partners with fecundability (i.e., the per-cycle probability of conception), adjusting for potential confounders. COVID-19 vaccination was not appreciably associated with fecundability in either partner (female fecundability ratio (FR) = 1.08, 95% confidence interval (CI): 0.95, 1.23; male FR = 0.95, 95% CI: 0.83, 1.10). Female SARS-CoV-2 infection was not strongly associated with fecundability (FR = 1.07, 95% CI: 0.87, 1.31). Male infection was associated with a transient reduction in fecundability (for infection within 60 days, FR = 0.82, 95% CI: 0.47, 1.45; for infection after 60 days, FR = 1.16, 95% CI: 0.92, 1.47). These findings indicate that male SARS-CoV-2 infection may be associated with a short-term decline in fertility and that COVID-19 vaccination does not impair fertility in either partner. 
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