Amelia K. Wesselink

Design and Conduct of an Internet-Based Preconception Cohort Study in North America: Pregnancy Study Online.

BACKGROUND We launched the Boston University Pregnancy Study Online (PRESTO) to assess the feasibility of carrying out an Internet-based preconception cohort study in the US and Canada. METHODS We recruited female participants age 21-45 and their male partners through Internet advertisements, word of mouth, and flyers. Female participants were randomised with 50% probability to receive a subscription to FertilityFriend.com (FF), a web-based programme that collects real-time data on menstrual characteristics. We compared recruitment methods within PRESTO, assessed the cost-efficiency of PRESTO relative to its Danish counterpart (Snart-Gravid), and validated retrospectively reported date of last menstrual period (LMP) against the FF data. RESULTS After 99 weeks of recruitment (2013-15), 2421 women enrolled; 1384 (57%) invited their male partners to participate, of whom 693 (50%) enrolled. Baseline characteristics were balanced across randomisation groups. Cohort retention was similar among those randomised vs. not randomised to FF (84% vs. 81%). At study enrollment, 56%, 22%, and 22% couples had been trying to conceive for < 3, 3-5, and ≥ 6 months, respectively. The cost per subject enrolled was

Caffeine and caffeinated beverage consumption and fecundability in a preconception cohort.

146 (2013 US

Dietary Fat Intake and Fecundability in 2 Preconception Cohort Studies

), which was similar to our companion Danish study and half that of a traditional cohort study. Among FF users who conceived, > 97% reported their LMP on the PRESTO questionnaire within 1 day of the LMP recorded via FF. CONCLUSIONS Use of the Internet as a method of recruitment and follow-up in a North American preconception cohort study was feasible and cost-effective.

Depression, anxiety, and psychotropic medication use and fecundability:

Caffeine is an adenosine receptor antagonist that may influence fertility by affecting ovulation, menstrual characteristics, or sperm quality. We studied the association between female and male preconception caffeine intake and fecundability in a North American prospective cohort study of 2135 pregnancy planners. Frequency of caffeinated beverage intake was self-reported at baseline. Outcome data were updated every 8 weeks until reported pregnancy; censoring occurred at 12 months. Adjusted fecundability ratios (FR) and 95% confidence intervals (CI) were estimated using proportional probabilities regression. Total caffeine intake among males, but not females, was associated with fecundability (FR for ≥300 vs. <100mg/day caffeine among males=0.72, 95% CI=0.54-0.96), although the association was not monotonic. With respect to individual beverages, caffeinated tea intake was associated with slight reductions in fecundability among females, and caffeinated soda and energy drink intake were associated with reduced fecundability among males.

Age and fecundability in a North American preconception cohort study

The association between dietary fat and fertility is not well studied. We evaluated intakes of total fat, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, trans fatty acids (TFA), ω-3 fatty acids, and ω-6 fatty acids in relation to fecundability in Danish and North American preconception cohort studies. Women who were attempting to become pregnant completed a validated food frequency questionnaire at baseline. Pregnancy status was updated bimonthly for 12 months or until pregnancy. Fecundability ratios (FR) and 95% confidence intervals were estimated using multivariable proportional probabilities regression. Intakes of total fat and saturated, monounsaturated, polyunsaturated, and ω-6 fatty acids were not appreciably associated with fecundability. TFA intake was associated with reduced fecundability in North American women (for the fourth quartile vs. the first, FR = 0.86, 95% confidence interval (CI): 0.71, 1.04) but not Danish women (for the fourth quartile vs. the first, FR = 1.04, 95% CI: 0.86, 1.25), though intake among Danish women was low. In North America, ω-3 fatty acid intake was associated with higher fecundability, but there was no dose-response relationship (among persons who did not use fish oil supplements: for the fourth quartile vs. the first, FR = 1.40, 95% CI: 1.13, 1.73); no association was found in Danish women, among whom low intake was rare. In the present study, high TFA intake and low ω-3 fatty acid intake were associated with reduced fecundity.

Dairy intake and fecundability in 2 preconception cohort studies.

BACKGROUND The literature regarding the associations between depression, anxiety, and fecundity is inconsistent. While cross-sectional studies suggest that depression and/or anxiety may adversely affect fecundity, the sole cohort study showed only a small association. OBJECTIVE We sought to evaluate the association of self-reported depressive symptoms, self-reported diagnoses of depression and anxiety, and psychotropic medication use with fecundability in a prospective cohort study. STUDY DESIGN Data were derived from Pregnancy Study Online (PRESTO), an Internet-based preconception cohort study of couples attempting to conceive in the United States and Canada. At baseline, female participants completed a survey that assessed demographic information, history of physician-diagnosed depression and anxiety, self-reported depressive symptoms (assessed by the Major Depression Inventory), and use of psychotropic medications. Women completed follow-up surveys every 8 weeks for up to 12 months or until reported conception to assess changes in exposures and pregnancy status. We estimated fecundability ratios and 95% confidence intervals using proportional probabilities regression models. The analysis was restricted to 2146 women who had been attempting to conceive for ≤6 cycles at study entry. RESULTS Severe depressive symptoms at baseline, regardless of treatment, were associated with decreased fecundability compared with no or low depressive symptoms (fecundability ratio, 0.62; 95% confidence interval, 0.43-0.91). The fecundability ratio associated with a 10-unit increase in Major Depression Inventory score was 0.90 (95% confidence interval, 0.83-0.97). Women who reported moderate to severe depressive symptoms and had never received psychotropic medications (fecundability ratio, 0.69; 95% confidence interval, 0.48-0.99) or who were currently being treated with psychotropic medications (fecundability ratio, 0.72; 95% confidence interval, 0.44-1.20) had decreased fecundability relative to women who had no/mild depressive symptoms and had never used psychotropic medications. Former users of psychotropic medications had increased fecundability regardless of the presence of no/mild depressive symptoms (fecundability ratio, 1.22; 95% confidence interval, 1.06-1.39) or moderate to severe depressive symptoms (fecundability ratio, 1.18; 95% confidence interval, 0.80-1.76). CONCLUSION We found an inverse association between depressive symptoms and fecundability, independent of psychotropic medication use. Use of psychotropic medications did not appear to harm fecundability.

Preconception use of pain-relievers and time-to-pregnancy: a prospective cohort study

Background There is a well‐documented decline in fertility treatment success with increasing female age; however, there are few preconception cohort studies that have examined female age and natural fertility. In addition, data on male age and fertility are inconsistent. Given the increasing number of couples who are attempting conception at older ages, a more detailed characterization of age‐related fecundability in the general population is of great clinical utility. Objective The purpose of this study was to examine the association between female and male age with fecundability. Study Design We conducted a web‐based preconception cohort study of pregnancy planners from the United States and Canada. Participants were enrolled between June 2013 and July 2017. Eligible participants were 21–45 years old (female) or ≥21 years old (male) and had not been using fertility treatments. Couples were followed until pregnancy or for up to 12 menstrual cycles. We analyzed data from 2962 couples who had been trying to conceive for ≤3 cycles at study entry and reported no history of infertility. We used life‐table methods to estimate the unadjusted cumulative pregnancy proportion at 6 and 12 cycles by female and male age. We used proportional probabilities regression models to estimate fecundability ratios, the per‐cycle probability of conception for each age category relative to the referent (21–24 years old), and 95% confidence intervals. Results Among female patients, the unadjusted cumulative pregnancy proportion at 6 cycles of attempt time ranged from 62.0% (age 28–30 years) to 27.6% (age 40–45 years); the cumulative pregnancy proportion at 12 cycles of attempt time ranged from 79.3% (age 25–27 years old) to 55.5% (age 40–45 years old). Similar patterns were observed among male patients, although differences between age groups were smaller. After adjusting for potential confounders, we observed a nearly monotonic decline in fecundability with increasing female age, with the exception of 28–33 years, at which point fecundability was relatively stable. Fecundability ratios were 0.91 (95% confidence interval, 0.74–1.11) for ages 25–27, 0.88 (95% confidence interval, 0.72–1.08) for ages 28–30, 0.87 (95% confidence interval, 0.70–1.08) for ages 31–33, 0.82 (95% confidence interval, 0.64–1.05) for ages 34–36, 0.60 (95% confidence interval, 0.44–0.81) for ages 37–39, and 0.40 (95% confidence interval, 0.22–0.73) for ages 40–45, compared with the reference group (age, 21–24 years). The association was stronger among nulligravid women. Male age was not associated appreciably with fecundability after adjustment for female age, although the number of men >45 years old was small (n=37). Conclusion In this preconception cohort study of North American pregnancy planners, increasing female age was associated with an approximately linear decline in fecundability. Although we found little association between male age and fecundability, the small number of men in our study >45 years old limited our ability to draw conclusions on fecundability in older men.

Marijuana use and fecundability in a North American preconception cohort study

BACKGROUND Animal studies have shown that a high intake of galactose, a breakdown product of lactose, increases ovarian toxicity. Few epidemiologic studies, to our knowledge, have examined the association between dairy intake and fertility, and they have had conflicting findings. OBJECTIVE We prospectively evaluated dairy intake in relation to fecundability among women who were planning for pregnancy. DESIGN Data were derived from preconception cohort studies in Denmark (Snart Foraeldre) and North America [PRESTO (Pregnancy Study Online)] in which women completed a validated food-frequency questionnaire 10 d after enrollment. The dietary intake of dairy foods and their constituents was calculated based on reported frequencies, mean serving sizes, and standard recipes for mixed foods. Outcome data were updated every 8 wk for 12 mo or until reported conception. Analyses were restricted to 2426 women attempting pregnancy for ≤6 cycles at study entry. Fecundability ratios (FRs) and 95% CIs were estimated with the use of proportional probabilities regression models adjusted for potential confounders. RESULTS FRs for total dairy intake (≥18 compared with <7 servings/wk) were 1.37 (95% CI: 1.05, 1.78) among 1126 Snart Foraeldre participants and 1.04 (95% CI: 0.78, 1.38) among 1300 PRESTO participants (pooled FR: 1.11; 95% CI: 0.94, 1.31). The elevated FR for total dairy intake among Snart Foraeldre participants was limited to milk consumption and found only among women aged <30 y. There was no clear association between low- or high-fat dairy intake and fecundability in either cohort. Although there was little evidence of an association between dietary intake of calcium, potassium, magnesium, or vitamin D and fecundability, a greater consumption of phosphorus and lactose was associated with slightly higher fecundability in both cohorts. CONCLUSIONS Associations between dairy intake and fecundability were generally small and inconsistent across cohorts. Our findings do not support the hypotheses that a greater consumption of high-fat dairy improves fertility or that a greater consumption of lactose or low-fat dairy harms fertility.

Exposure to tetrachloroethylene-contaminated drinking water and time to pregnancy

STUDY QUESTION To what extent is preconception use of pain-relieving medication associated with female fecundability? SUMMARY ANSWER Women who used naproxen or opioids had slightly lower fecundability than women who did not use any pain-relieving medications; use of acetaminophen, aspirin and ibuprofen was not appreciably associated with fecundability. WHAT IS KNOWN ALREADY Over-the-counter pain-relieving medications are commonly used by women of reproductive age in the USA. Studies investigating the effects of pain-relieving medication use on ovulation, implantation and fecundability have shown conflicting results. STUDY DESIGN, SIZE, DURATION We analyzed data from an internet-based prospective cohort study of 2573 female pregnancy planners aged 21–45 years from the USA and Canada. Participants were enrolled and followed from June 2013 through September 2015. Participants completed a baseline questionnaire and bimonthly follow-up questionnaires until a reported pregnancy or for 12 months, whichever occurred first. Over 80% of participants completed at least one follow-up questionnaire. PARTICIPANTS/MATERIALS, SETTING, METHODS Use of pain-relieving medication during the past month was assessed at baseline and on each follow-up questionnaire. Medications were categorized according to type (acetaminophen, aspirin, ibuprofen, naproxen and opioids) and total monthly dose. Self-reported pregnancy was assessed at each follow-up. Multivariable-adjusted fecundability ratios (FRs) and 95% CI were calculated using proportional probabilities regression. Models were adjusted for demographic, lifestyle and anthropometric factors; reproductive history; gynecologic morbidity; and indications for use of pain medications. Models were also run with and without adjustment for parity. After restricting to women with 6 or fewer months of attempt time at study entry, 1763 were included in the analyses. MAIN RESULTS AND THE ROLE OF CHANCE At baseline, 1279 (73%) women reported using ≥1 pain-relieving medications in the previous month. When compared with non-use of pain-relieving medications, FRs for use of naproxen and opioids at baseline were 0.78 (95% CI: 0.64–0.97) and 0.81 (95% CI: 0.60–1.10), respectively. A dose–response relation was observed between naproxen use and fecundability; FRs for use of <1500 and ≥1500 mg of naproxen were 0.85 (95% CI: 0.68–1.07) and 0.58 (95% CI: 0.36–0.94), respectively. Small numbers (n = 74) precluded the examination of opioid use by dose. Overall, there was little evidence of an association between fecundability and acetaminophen (FR 1.04, 95% CI: 0.92–1.18), aspirin (FR 1.00, 95% CI: 0.80–1.25), or ibuprofen (FR 1.00, 95% CI: 0.89–1.11). Similar results were observed when exposure information was updated over time. LIMITATIONS, REASONS FOR CAUTION Numbers of opioid users were small. Information collected on reason for use of pain medications was not specific to each type of pain medication. Therefore, we cannot rule out confounding by indication as an explanation of these results. WIDER IMPLICATIONS OF THE FINDINGS Use of naproxen and opioids was associated with a small reduction in fecundability, but there was little association between other pain-relieving medications and fecundability. STUDY FUNDING/COMPETING INTEREST(S) This study was supported through funds provided by National Institute of Child Health and Human Development, National Institute of Health (R21 HD072326, T32 HD052458). The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER Not applicable.

Mental health, psychotropic medication use, and menstrual cycle characteristics

Background The influence of marijuana use on human fertility has not been well studied. We evaluated the association between female and male use of marijuana and fecundability in Pregnancy Study Online, a prospective cohort of North American couples. Methods Female participants completed a baseline questionnaire on which they reported lifestyle and behavioural factors, including frequency of marijuana use within the previous 2 months. Male partners completed an optional baseline questionnaire on similar factors, including marijuana use. Women completed follow-up questionnaires every 8 weeks for 12 months or until pregnancy, initiation of fertility treatment or loss to follow-up, whichever came first. The analysis was restricted to 4194 women (1125 couples) with ≤6 cycles of pregnancy attempt time at study enrolment (2013–2017). Fecundability ratios (FR) and 95% CIs were estimated using proportional probabilities regression models, with adjustment for potential confounders. Results Men (14.2%) were more likely than women (11.6%) to be marijuana users. FRs for female marijuana use <1 and ≥1 time/week relative to non-use were 0.99 (95% CI 0.85 to 1.16) and 0.98 (95% CI 0.80 to 1.20), respectively. FRs for male marijuana use <1 and ≥1 time/week relative to non-use were 0.87 (95% CI 0.66 to 1.15) and 1.24 (95% CI 0.90 to 1.70), respectively. Associations for frequent marijuana use (≥1 time/week) were attenuated among non-smoking men (FR=1.21, 95% CI 0.84 to 1.74), but stronger among men reporting intercourse ≥4 times/week (FR=1.35, 95% CI 0.72 to 2.53). Conclusions In this preconception cohort study, there was little overall association between female or male marijuana use and fecundability.