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1. Association of male fatty acid intake with fecundability among couples planning pregnancy

   https://doi.org/10.1093/humrep/dead100  

   Geller, Ruth J; Wesselink, Amelia K; Koenig, Martha R; Eisenberg, Michael L; Tucker, Katherine L; Hatch, Elizabeth E; Wise, Lauren A (May 2023, Human Reproduction)

   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. Intergenerational Associations between Parents’ and Children’s Adverse Childhood Experience Scores

   https://doi.org/10.3390/children8090747  

   Schickedanz, Adam; Escarce, José J.; Halfon, Neal; Sastry, Narayan; Chung, Paul J. (September 2021, Children)

   Background: Adverse childhood experiences (ACEs) are stressful childhood events associated with behavioral, mental, and physical illness. Parent experiences of adversity may indicate a child’s adversity risk, but little evidence exists on intergenerational links between parents’ and children’s ACEs. This study examines these intergenerational ACE associations, as well as parent factors that mediate them. Methods: The Panel Study of Income Dynamics (PSID) 2013 Main Interview and the linked PSID Childhood Retrospective Circumstances Study collected parent and child ACE information. Parent scores on the Aggravation in Parenting Scale, Parent Disagreement Scale, and the Kessler-6 Scale of Emotional Distress were linked through the PSID 1997, 2002, and 2014 PSID Childhood Development Supplements. Multivariate linear and multinomial logistic regression models estimated adjusted associations between parent and child ACE scores. Results: Among 2205 parent-child dyads, children of parents with four or more ACEs had 3.25-fold (23.1% [95% CI 15.9–30.4] versus 7.1% [4.4–9.8], p-value 0.001) higher risk of experiencing four or more ACEs themselves, compared to children of parents without ACEs. Parent aggravation, disagreement, and emotional distress were partial mediators. Conclusions: Parents with higher ACE scores are far more likely to have children with higher ACEs. Addressing parenting stress, aggravation, and discord may interrupt intergenerational adversity cycles. 

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3. Electronic Cigarettes and Fecundability: Results From a Prospective Preconception Cohort Study

   https://doi.org/10.1093/aje/kwaa067  

   Harlow, Alyssa F; Hatch, Elizabeth E; Wesselink, Amelia K; Rothman, Kenneth J; Wise, Lauren A (May 2020, American Journal of Epidemiology)

   Abstract Although electronic cigarette (e-cigarette) aerosol contains similar toxicants to combustible cigarettes, few studies have examined their influence on fecundability. We assessed the association between e-cigarette use and fecundability, overall and according to combustible cigarette smoking history, in a cohort of 4,586 North American women (aged 21–45 years) enrolled during 2017–2020 in Pregnancy Study Online, a Web-based prospective preconception study. Women reported current and former e-cigarette use on baseline and follow-up questionnaires, and they completed bimonthly follow-up questionnaires until self-reported pregnancy or censoring. Fecundability ratios and 95% confidence intervals were calculated using proportional probabilities models, controlling for potential confounders. Overall, 17% of women had ever used e-cigarettes and 4% were current users. Compared with never use of e-cigarettes, current e-cigarette use was associated with slightly lower fecundability (fecundability ratio = 0.84, 95% confidence interval (CI): 0.67, 1.06). Compared with current nonusers of e-cigarettes and combustible cigarettes, fecundability ratios were 0.83 (95% CI: 0.54, 1.29) for current dual users of e-cigarettes and combustible cigarettes, 0.91 (95% CI: 0.70, 1.18) for current e-cigarette users who were nonsmokers of combustible cigarettes, and 1.01 (95% CI: 0.85, 1.20) for nonusers of e-cigarettes who were current smokers of combustible cigarettes. Current e-cigarette use was associated with slightly reduced fecundability, but estimates of its independent and joint associations with combustible cigarette smoking were inconsistent and imprecise. 

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4. Male cellular telephone exposure, fecundability, and semen quality: results from two preconception cohort studies

   https://doi.org/10.1093/humrep/deab001  

   Hatch, E E; Willis, S K; Wesselink, A K; Mikkelsen, E M; Eisenberg, M L; Sommer, G J; Sorensen, H T; Rothman, K J; Wise, L A (February 2021, Human Reproduction)

   Abstract STUDY QUESTION To what extent is exposure to cellular telephones associated with male fertility? SUMMARY ANSWER Overall, we found little association between carrying a cell phone in the front pants pocket and male fertility, although among leaner men (BMI <25 kg/m2), carrying a cell phone in the front pants pocket was associated with lower fecundability. WHAT IS KNOWN ALREADY Some studies have indicated that cell phone use is associated with poor semen quality, but the results are conflicting. STUDY DESIGN, SIZE, DURATION Two prospective preconception cohort studies were conducted with men in Denmark (n = 751) and in North America (n = 2349), enrolled and followed via the internet from 2012 to 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS On the baseline questionnaire, males reported their hours/day of carrying a cell phone in different body locations. We ascertained time to pregnancy via bi-monthly follow-up questionnaires completed by the female partner for up to 12 months or until reported conception. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs) for the association between male cell phone habits and fecundability, focusing on front pants pocket exposure, within each cohort separately and pooling across the cohorts using a fixed-effect meta-analysis. In a subset of participants, we examined selected semen parameters (semen volume, sperm concentration and sperm motility) using a home-based semen testing kit. MAIN RESULTS AND THE ROLE OF CHANCE There was little overall association between carrying a cell phone in a front pants pocket and fecundability: the FR for any front pants pocket exposure versus none was 0.94 (95% CI: 0.0.83–1.05). We observed an inverse association between any front pants pocket exposure and fecundability among men whose BMI was <25 kg/m2 (FR = 0.72, 95% CI: 0.59–0.88) but little association among men whose BMI was ≥25 kg/m2 (FR = 1.05, 95% CI: 0.90–1.22). There were few consistent associations between cell phone exposure and semen volume, sperm concentration, or sperm motility. LIMITATIONS, REASONS FOR CAUTION Exposure to radiofrequency radiation from cell phones is subject to considerable non-differential misclassification, which would tend to attenuate the estimates for dichotomous comparisons and extreme exposure categories (e.g. exposure 8 vs. 0 h/day). Residual confounding by occupation or other unknown or poorly measured factors may also have affected the results. WIDER IMPLICATIONS OF THE FINDINGS Overall, there was little association between carrying one’s phone in the front pants pocket and fecundability. There was a moderate inverse association between front pants pocket cell phone exposure and fecundability among men with BMI <25 kg/m2, but not among men with BMI ≥25 kg/m2. Although several previous studies have indicated associations between cell phone exposure and lower sperm motility, we found few consistent associations with any semen quality parameters. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by the National Institutes of Health, grant number R03HD090315. In the last 3 years, PRESTO has received in-kind donations from Sandstone Diagnostics (for semen kits), Swiss Precision Diagnostics (home pregnancy tests), Kindara.com (fertility app), and FertilityFriend.com (fertility app). Dr. L.A.W. is a fibroid consultant for AbbVie, Inc. Dr. H.T.S. reports that the Department of Clinical Epidemiology is involved in studies with funding from various companies as research grants to and administered by Aarhus University. None of these studies are related to the current study. Dr. M.L.E. is an advisor to Sandstone Diagnostics, Ro, Dadi, Hannah, and Underdog. Dr. G.J.S. holds ownership in Sandstone Diagnostics Inc., developers of the Trak Male Fertility Testing System. In addition, Dr. G.J.S. has a patent pending related to Trak Male Fertility Testing System issued. TRIAL REGISTRATION NUMBER N/A 

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5. Antibiotics and fecundability among female pregnancy planners: a prospective cohort study

   https://doi.org/10.1093/humrep/deab173  

   Crowe, Holly Michelle; Wesselink, Amelia Kent; Wise, Lauren Anne; Wang, Tanran R; Horsburgh, Charles Robert; Mikkelsen, Ellen Margrethe; Hatch, Elizabeth Elliott (July 2021, Human Reproduction)

   Abstract STUDY QUESTION To what extent is female preconception antibiotic use associated with fecundability? SUMMARY ANSWER Preconception antibiotic use overall was not appreciably associated with fecundability. WHAT IS KNOWN ALREADY Antibiotics are commonly used by women and are generally thought to be safe for use during pregnancy. However, little is known about possible effects of antibiotic use on fecundability, the per-cycle probability of conception. Previous research on this question has been limited to occupational rather than therapeutic exposure. STUDY DESIGN, SIZE, DURATION We analyzed data from an Internet-based preconception cohort study of 9524 female pregnancy planners aged 21–45 years residing in the USA and Canada who had been attempting to conceive for six or fewer cycles at study entry. Participants enrolled between June 2013 and September 2020 and completed baseline and bimonthly follow-up questionnaires for up to 12 months or until a reported pregnancy, whichever came first. The questions pertaining to antibiotic type and indication were added to the PRESTO questionnaires in March 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS We assessed antibiotic use in the previous 4 weeks at baseline and on each follow-up questionnaire. Participants provided the name of the specific antibiotic and the indication for use. Antibiotics were classified based on active ingredient (penicillins, macrolides, nitrofurantoin, nitroimidazole, cephalosporins, sulfonamides, quinolones, tetracyclines, lincosamides), and indications were classified by type of infection (respiratory, urinary tract, skin, vaginal, pelvic, and surgical). Participants reported pregnancy status on follow-up questionnaires. We used proportional probabilities regression to estimate fecundability ratios (FR), the per-cycle probability of conception comparing exposed with unexposed individuals, and 95% confidence intervals (CI), adjusting for sociodemographics, lifestyle factors, and reproductive history. MAIN RESULTS AND THE ROLE OF CHANCE Overall, women who used antibiotics in the past 4 weeks at baseline had similar fecundability to those who had not used antibiotics (FR: 0.98, 95% CI: 0.89–1.07). Sulfonamides and lincosamides were associated with slightly increased fecundability (FR: 1.39, 95% CI: 0.90–2.15, and FR: 1.58 95% CI: 0.96–2.60, respectively), while macrolides were associated with slightly reduced fecundability (FR: 0.70, 95% CI: 0.47–1.04). Analyses of the indication for antibiotic use suggest that there is likely some confounding by indication. LIMITATIONS, REASONS FOR CAUTION Findings were imprecise for some antibiotic classes and indications for use owing to small numbers of antibiotic users in these categories. There are likely heterogeneous effects of different combinations of indications and treatments, which may be obscured in the overall null results, but cannot be further elucidated in this analysis. WIDER IMPLICATIONS OF THE FINDINGS There is little evidence that use of most antibiotics is associated with reduced fecundability. Antibiotics and the infections they treat are likely associated with fecundability through differing mechanisms, resulting in their association with increased fecundability in some circumstances and decreased fecundability in others. STUDY FUNDING/COMPETING INTEREST(S) This study was supported through funds provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (R01-HD086742, R21-HD072326). L.A.W. has received in-kind donations from Swiss Precision Diagnostics, Sandstone Diagnostics, Fertility Friend, and Kindara for primary data collection in PRESTO. The other authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER N/A. 

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