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STUDY QUESTION To what extent is male fatty acid intake associated with fecundability among couples planning pregnancy? SUMMARY ANSWER We 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 ALREADY Male 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, DURATION We 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, METHODS Participants 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 CHANCE Among 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 CAUTION Dietary 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 FINDINGS Our 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 NUMBER N/A.

Chemical hair straighteners (“relaxers”) are used by millions of North Americans, particularly women of color. Hair relaxers may contain endocrine-disrupting compounds, which can harm fertility. We evaluated the association between hair relaxer use and fecundability among 11,274 participants from Pregnancy Study Online (PRESTO), a North American preconception cohort study. During 2014-2022, participants completed a baseline questionnaire on which they reported their history of relaxer use and completed follow-up questionnaires every 8 weeks for 12 months or until pregnancy, whichever came first. We used multivariable-adjusted proportional probabilities regression models to estimate fecundability ratios (FR) and 95% confidence intervals (CI). Relative to never use, fecundability was lower among current (FR=0.81, 95% CI: 0.64-1.03) and former (FR=0.89, 95% CI: 0.81-0.98) users of hair relaxers. FRs for first use of hair relaxers at age <10, 10-19, and ≥20 years were 0.73 (95% CI: 0.55-0.96), 0.93 (95% CI: 0.83-1.04), and 0.85 (95% CI: 0.74-0.98), respectively. Fecundability was lowest among those with longer durations of use (≥10 years vs. never: FR=0.71, 95% CI: 0.54-0.91) and more frequent use (≥5 times/year vs. never: FR=0.82, 95% CI: 0.60-1.11), but associations were non-monotonic. In this preconception cohort study, use of chemical hair straighteners was associated with slightly reduced fecundability.

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BackgroundProspective cohort studies that enroll participants before conception are crucial for deepening scientific understanding of how the preconception environment influences reproductive outcomes. While web-based research methods provide efficient and effective strategies to collect questionnaire-based data, few of these studies incorporate biospecimen collection, which can enhance the validity of exposure assessment. There is limited literature on the feasibility and cost-effectiveness of collecting biospecimens in web-based preconception cohort studies.MethodsWe evaluated the feasibility and cost-effectiveness of in-clinic and mail-based biospecimen collection in Pregnancy Study Online (PRESTO), a North American web-based preconception cohort study. Both members of the couple were eligible to participate if their conception attempt time was ≤3 months at enrollment. We invited study participants from the Boston, MA and Detroit, MI metropolitan areas to attend a study visit and provide urine and blood (hereafter “in-clinic protocol”). We invited all other participants to complete mail-based collection of urine and blood spots (hereafter “mail-based protocol”). We compared overall consent and protocol completion rates, demographic characteristics of those who consented and completed either of the protocols, and costs between mail-based and in-clinic protocols for biospecimen collection. Finally, we described logistical challenges pertaining to reliance on mail-based delivery of time-sensitive biospecimens compared with in-clinic methods.ResultsDuring January 2022-July 2022, 69% of female participants (134/195) and 42% of male participants (31/74) consented to participate in the mail-based protocol. Consent rates for the in-clinic protocol were 39% for female participants (289/739 during March 2014-July 2022) and 25% for male participants (40/157 during March 2017-July 2022). Participants who consented to participate were generally of higher socioeconomic position than non-participants. Deviations from the protocol occurred more frequently within the mail-based protocol but were easily corrected. The cost per participant enrolled was similar across protocols (mail-based: $276.14 vs. in-clinic: $270.38).ConclusionsOur results indicate that mail-based collection of biospecimens may create opportunities to recruit a larger and more geographically diverse participant population at a comparable cost-per-participant enrolled to in-clinic methods.