Preconception use of antibiotics and fecundability: a Danish prospective cohort study.

OBJECTIVE: To assess the association between preconception antibiotic use and fecundability, the per menstrual cycle probability of conception. DESIGN: SnartForaeldre.dk, a Danish prospective cohort study of women trying to conceive (2007-2020). SETTING: Not applicable. SUBJECT(S): 9462 female participants, median age 29 years at enrollment. EXPOSURE: Antibiotic use was defined by filled prescriptions retrieved from the Danish National Prescription Registry, using Anatomical Therapeutic Chemical codes, and modeled as time-varying (menstrual cycle-varying) exposure. MAIN OUTCOME MEASURE(S): Pregnancy status was reported on female follow-up questionnaires every 8 weeks for up to 12 months or until conception. Fecundability ratios (FR) and 95% confidence intervals (CI) were computed using proportional probabilities regression models, with adjustment for age, partner age, education, smoking, folic acid supplementation, body mass index, parity, cycle regularity, timing of intercourse, and sexually transmitted infections. RESULT(S): During all cycles of observation, the percentage of participants filing at least 1 antibiotic prescription was 11.9%; 8.6% had a prescription for penicillins, 2.1% for sulfonamides, and 1.8% for macrolides. Based on life-table methods, 86.5% of participants conceived within 12 cycles of follow-up. Recent preconception antibiotic use was associated with reduced fecundability (≥1 prescription vs. none: adjusted FR = 0.86; 95% CI, 0.76-0.99). For participants using penicillins, sulfonamides, or macrolides, the adjusted FRs were 0.97 (95% CI, 0.83-1.12), 0.68 (95% CI, 0.47-0.98), and 0.59 (95% CI, 0.37-0.93), respectively. CONCLUSION(S): Preconception use of antibiotics, specifically sulfonamides and macrolides, was associated with decreased fecundability compared with no use. The observed associations may be explained plausibly by confounding by indication, as we lacked data on indications for the prescribed antibiotics. Consequently, we cannot separate the effect of the medication from the effect of the underlying infection.

Association of Asthma Diagnosis and Medication Use with Fecundability: A Prospective Cohort Study.

PURPOSE: Asthma has been positively associated with irregular menses and infertility in some studies, but data are limited on the relation between asthma medication use and fecundability (i.e., average per-cycle probability of conception among non-contracepting couples). This study examines the extent to which a history of asthma, asthma medication use, and age at first asthma diagnosis are associated with fecundability among female pregnancy planners. PARTICIPANTS AND METHODS: Pregnancy Study Online (PRESTO) is an ongoing, web-based preconception cohort study of couples aged 21-45 years from North America. Between July 2013 and July 2019, a total of 10,436 participants enrolled in PRESTO, and 8286 were included in the present analysis. At study enrollment, women reported whether they had ever been diagnosed with asthma and, if so, the year they were first diagnosed. Women who reported ever being diagnosed with asthma were asked about medication use, including medication type and frequency of use. Participants completed follow-up questionnaires every 8 weeks for up to 12 months or until pregnancy. Proportional probabilities regression models were used to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), adjusting for potential confounders. Fecundability ratios below 1.00 indicate reduced probability of conception. RESULTS: There was little association between a history of asthma diagnosis or asthma medication use and fecundability. Compared with no history of asthma, the FR for ever-diagnosis of asthma with medication use was 1.02 (95% CI: 0.91-1.15) and for ever-diagnosis of asthma without medication use was 1.00 (95% CI: 0.91-1.09). Highest intensity asthma medication use (daily plus extra dosing for symptoms), combination inhaled corticosteroid and long-acting beta-agonist inhaler use, and a first diagnosis of asthma after age 17 years were associated with small reductions in fecundability. CONCLUSION: The present study provides little evidence that asthma or asthma medication use is adversely associated with fecundability.

Fecundability in relation to use of fertility awareness indicators in a North American preconception cohort study.

OBJECTIVE: To quantify the frequency of use of selected fertility awareness indicators and to assess their influence on fecundability. DESIGN: Web-based prospective cohort study. SETTING: Not applicable. PATIENT(S): Female pregnancy planners, aged 21-45 years, attempting conception for ≤6 cycles at study entry. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We ascertained time to pregnancy, in menstrual cycles, with bimonthly questionnaires. We estimated adjusted fecundability ratios (FRs) and confidence intervals (CIs) using proportional probabilities models, controlling for age, income, education, smoking, intercourse frequency, and other lifestyle and reproductive factors. RESULT(S): A total of 5,688 women were analyzed, with a mean age of 29.9 years and mean time trying of 2.1 cycles at baseline; 30% had ever been pregnant. At baseline, 75% were using one or more fertility indicators (counting days or charting menstrual cycles [71%], measuring basal body temperature [BBT, 21%], monitoring cervical fluid [39%], using urine LH tests [32%], or feeling for changes in position of the cervix [12%]). Women using any fertility indicator at baseline had higher subsequent fecundability (adjusted FR 1.25, 95% CI 1.16-1.35) than those not using any fertility indicators. For each individual indicator, adjusted FRs ranged from 1.28-1.36, where 1.00 would indicate no relation with fecundability. The adjusted FR for women using a combination of charting days, cervical fluid, and urine LH was 1.48 (95% CI 1.31-1.67) relative to women using no fertility indicators. CONCLUSION(S): In a North American preconception cohort study, use of fertility indicators indicating the fertile window was common, and was associated with greater fecundability.

Female sleep patterns, shift work, and fecundability in a North American preconception cohort study.

OBJECTIVE: To prospectively evaluate the association between female sleep patterns, shift work, and fecundability. DESIGN: Web-based preconception cohort study, Pregnancy Study Online (PRESTO). SETTING: Not applicable. PATIENT(S): North American Women aged 21-45 years attempting pregnancy. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): At baseline, self-reported average sleep duration per 24-hour period in the previous month, the frequency of trouble sleeping within the last 2 weeks (as measured by the Major Depression Inventory), and shift work patterns. Pregnancy status determined by follow-up questionnaires completed every 8 weeks for up to 12 months or until conception. RESULT(S): The analyses were restricted to 6,873 women attempting pregnancy for ≤6 months at enrollment from June 2013 through September 2018. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), adjusting for potential confounders. Relative to 8 hours of sleep per day, FRs for <6, 6, 7, and ≥9 hours of sleep/day were 0.89 (95% CI, 0.75-1.06), 0.95 (95% CI, 0.86-1.04), 0.99 (95% CI, 0.92-1.06), and 0.96 (95% CI, 0.84-1.10), respectively. Compared with no trouble sleeping, FRs for trouble sleeping <50% of the time or trouble sleeping >50% of the time were 0.93 (95% CI, 0.88-1.00) and 0.87 (95% CI, 0.79-0.95), respectively. The results were slightly stronger among women with higher depressive symptoms and perceived stress levels. There was no association between shift work and fecundability. CONCLUSION(S): Trouble sleeping at night was associated with modestly reduced fecundability. A weaker inverse association was observed between shorter sleep duration and fecundability.

Male sleep duration and fecundability in a North American preconception cohort study.

OBJECTIVE: To evaluate prospectively the association between male sleep duration and fecundability. DESIGN: Pregnancy Online Study (PRESTO), a Web-based prospective cohort study of North American couples enrolled during the preconception period (2013-2017). SETTING: Not applicable. PATIENT(S): Male participants were aged ≥21 years; female participants were aged 21-45 years. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): At enrollment, men reported their average nightly sleep duration in the previous month. Pregnancy status was updated on female follow-up questionnaires every 8 weeks for up to 12 months or until conception. Analyses were restricted to 1,176 couples who had been attempting to conceive for up to six cycles at enrollment. Proportional probabilities regression models were used to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), adjusting for potential confounders. RESULT(S): Relative to 8 hours per night of sleep, multivariable-adjusted FRs for <6, 6, 7, and ≥9 hours per night of sleep were 0.62 (95% CI 0.45-0.87), 1.06 (95% CI 0.87-1.30), 0.97 (95% CI 0.81-1.17), and 0.73 (95% CI 0.46-1.15), respectively. The association between short sleep duration (<6 hours per night) and fecundability was similar among men not working nights or rotating shifts (FR 0.60, 95% CI 0.41-0.88) and among men without a history of infertility (FR 0.62, 95% CI 0.44-0.87) and was stronger among fathers (FR 0.46, 95% CI 0.28-0.76). CONCLUSION(S): Short sleep duration in men was associated with reduced fecundability. Because male factor accounts for 50% of couple infertility, identifying modifiable determinants of infertility could provide alternatives to expensive fertility workups and treatments.