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Kenneth J. Rothman - One of the best experts on this subject based on the ideXlab platform.

  • pregravid contraceptive use and Fecundability prospective cohort study
    BMJ, 2020
    Co-Authors: Jennifer J Yland, Ellen M. Mikkelsen, Kenneth J. Rothman, Elizabeth E. Hatch, Henrik Toft Sørensen, Amelia K. Wesselink, Kathryn A Bresnick, Krista F Huybrechts
    Abstract:

    Abstract Objective To evaluate the association between pregravid use of a variety of contraceptive methods and subsequent Fecundability. Design Prospective cohort study. Setting Denmark and North America, 2007-19. Participants 17 954 women who had tried to conceive for up to six menstrual cycles at study entry. At baseline, participants reported their contraceptive histories, and personal, medical, and lifestyle characteristics. Main outcome measures Pregnancy, determined by bimonthly follow-up questionnaires for up to 12 months. Results Approximately 38% (n=6735) of participants had recently used oral contraceptives, 13% (n=2398) had used long acting reversible contraceptive methods, and 31% (n=5497) had used barrier methods. Women who had recently stopped using oral contraceptives, the contraceptive ring, and some long acting reversible contraceptive methods experienced short term delays in return of fertility compared with users of barrier methods. Use of injectable contraceptives was associated with decreased Fecundability compared with use of barrier methods (Fecundability ratio 0.65; 95% confidence interval 0.47 to 0.89). Users of injectable contraceptives had the longest delay in return of normal fertility (five to eight menstrual cycles), followed by users of patch contraceptives (four cycles), users of oral and ring contraceptives (three cycles), and users of hormonal and copper intrauterine devices and implant contraceptives (two cycles). Lifetime length of use of hormonal contraceptive methods was not associated with Fecundability. Conclusions Use of some hormonal contraceptive methods was associated with delays in return of fertility, with injectable contraceptives showing the longest delay. The findings indicated little or no lasting effect of long term use of these methods on Fecundability.

  • association between male use of pain medication and Fecundability
    American Journal of Epidemiology, 2020
    Co-Authors: Amelia K. Wesselink, Ellen M. Mikkelsen, Kenneth J. Rothman, Elizabeth E. Hatch, Tanran R Wang, Kathryn A Bresnick, Krista F Huybrechts, Lauren A. Wise
    Abstract:

    Administration of pain relievers has been associated with both lower and higher risks of adverse reproductive outcomes in animals. In the sole investigation of male pain-reliever use and human fertility carried out to date, Smarr et al. (Hum Reprod. 2016;31(9):2119-2127) found a 35% reduction in Fecundability among males with urinary acetaminophen concentrations in the highest quartile (>73.5 ng/mL) versus the lowest (<5.4 ng/mL). We analyzed data from 1,956 males participating in Pregnancy Study Online, a preconception cohort study of North American couples enrolled between 2013 and 2019. Males and females completed baseline questionnaires on sociodemographic characteristics, lifestyle, medication use, and medical history; females completed bimonthly follow-up questionnaires for up to 12 months. We categorized pain medications by active ingredient (ibuprofen, acetaminophen, naproxen, aspirin) and cumulative monthly dose. We used proportional probabilities models to calculate Fecundability ratios and 95% confidence intervals, adjusting for potential confounders. In the 4 weeks before baseline, 51.7% of males used pain medications. Adjusted Fecundability ratios were 1.02 for ibuprofen (95% confidence interval (CI): 0.91, 1.13), 0.89 for acetaminophen (95% CI: 0.77, 1.03), 1.07 for naproxen (95% CI: 0.85, 1.35), and 1.05 for aspirin (95% CI: 0.81, 1.35), as compared with nonuse of each medication. In this study, male use of pain medications at low doses was not notably associated with Fecundability.

  • Fecundability in relation to use of mobile computing apps to track the menstrual cycle
    Human Reproduction, 2020
    Co-Authors: Joseph B Stanford, Kenneth J. Rothman, Elizabeth E. Hatch, Sydney K Willis, Lauren A. Wise
    Abstract:

    STUDY QUESTION To what extent does the use of mobile computing apps to track the menstrual cycle and the fertile window influence Fecundability among women trying to conceive? SUMMARY ANSWER After adjusting for potential confounders, use of any of several different apps was associated with increased Fecundability ranging from 12% to 20% per cycle of attempt. WHAT IS KNOWN ALREADY Many women are using mobile computing apps to track their menstrual cycle and the fertile window, including while trying to conceive. STUDY DESIGN, SIZE, DURATION The Pregnancy Study Online (PRESTO) is a North American prospective internet-based cohort of women who are aged 21-45 years, trying to conceive and not using contraception or fertility treatment at baseline. PARTICIPANTS/MATERIALS, SETTING, METHODS We restricted the analysis to 8363 women trying to conceive for no more than 6 months at baseline; the women were recruited from June 2013 through May 2019. Women completed questionnaires at baseline and every 2 months for up to 1 year. The main outcome was Fecundability, i.e. the per-cycle probability of conception, which we assessed using self-reported data on time to pregnancy (confirmed by positive home pregnancy test) in menstrual cycles. On the baseline and follow-up questionnaires, women reported whether they used mobile computing apps to track their menstrual cycles ('cycle apps') and, if so, which one(s). We estimated Fecundability ratios (FRs) for the use of cycle apps, adjusted for female age, race/ethnicity, prior pregnancy, BMI, income, current smoking, education, partner education, caffeine intake, use of hormonal contraceptives as the last method of contraception, hours of sleep per night, cycle regularity, use of prenatal supplements, marital status, intercourse frequency and history of subfertility. We also examined the impact of concurrent use of fertility indicators: basal body temperature, cervical fluid, cervix position and/or urine LH. MAIN RESULTS AND THE ROLE OF CHANCE Among 8363 women, 6077 (72.7%) were using one or more cycle apps at baseline. A total of 122 separate apps were reported by women. We designated five of these apps before analysis as more likely to be effective (Clue, Fertility Friend, Glow, Kindara, Ovia; hereafter referred to as 'selected apps'). The use of any app at baseline was associated with 20% increased Fecundability, with little difference between selected apps versus other apps (selected apps FR (95% CI): 1.20 (1.13, 1.28); all other apps 1.21 (1.13, 1.30)). In time-varying analyses, cycle app use was associated with 12-15% increased Fecundability (selected apps FR (95% CI): 1.12 (1.04, 1.21); all other apps 1.15 (1.07, 1.24)). When apps were used at baseline with one or more fertility indicators, there was higher Fecundability than without fertility indicators (selected apps with indicators FR (95% CI): 1.23 (1.14, 1.34) versus without indicators 1.17 (1.05, 1.30); other apps with indicators 1.30 (1.19, 1.43) versus without indicators 1.16 (1.06, 1.27)). In time-varying analyses, results were similar when stratified by time trying at study entry (<3 vs. 3-6 cycles) or cycle regularity. For use of the selected apps, we observed higher Fecundability among women with a history of subfertility: FR 1.33 (1.05-1.67). LIMITATIONS, REASONS FOR CAUTION Neither regularity nor intensity of app use was ascertained. The prospective time-varying assessment of app use was based on questionnaires completed every 2 months, which would not capture more frequent changes. Intercourse frequency was also reported retrospectively and we do not have data on timing of intercourse relative to the fertile window. Although we controlled for a wide range of covariates, we cannot exclude the possibility of residual confounding (e.g. choosing to use an app in this observational study may be a marker for unmeasured health habits promoting Fecundability). Half of the women in the study received a free premium subscription for one of the apps (Fertility Friend), which may have increased the overall prevalence of app use in the time-varying analyses, but would not affect app use at baseline. Most women in the study were college educated, which may limit application of results to other populations. WIDER IMPLICATIONS OF THE FINDINGS Use of a cycle app, especially in combination with observation of one or more fertility indicators (basal body temperature, cervical fluid, cervix position and/or urine LH), may increase Fecundability (per-cycle pregnancy probability) by about 12-20% for couples trying to conceive. We did not find consistent evidence of improved Fecundability resulting from use of one specific app over another. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by grants, R21HD072326 and R01HD086742, from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, USA. In the last 3 years, Dr L.A.W. has served as a fibroid consultant for AbbVie.com. Dr L.A.W. has also received in-kind donations from Sandstone Diagnostics, Swiss Precision Diagnostics, FertilityFriend.com and Kindara.com for primary data collection and participant incentives in the PRESTO cohort. Dr J.B.S. reports personal fees from Swiss Precision Diagnostics, outside the submitted work. The remaining authors have nothing to declare. TRIAL REGISTRATION NUMBER N/A.

  • association of income and education with Fecundability in a north american preconception cohort
    Annals of Epidemiology, 2020
    Co-Authors: Nina L Schrager, Ellen M. Mikkelsen, Kenneth J. Rothman, Elizabeth E. Hatch, Amelia K. Wesselink, Tanran R Wang, Renee Boyntonjarrett, Lauren A. Wise
    Abstract:

    Abstract Purpose To evaluate socioeconomic determinants of Fecundability. Methods Among 8,654 female pregnancy planners from Pregnancy Study Online, a North American prospective cohort study (2013-2019), we examined associations between socioeconomic status and Fecundability (the per-cycle probability of conception). Information on income and education was collected via baseline questionnaire. Bimonthly follow-up questionnaires were used to ascertain pregnancy status. We estimated Fecundability ratios (FRs) and 95% confidence intervals (CI) using proportional probabilities regression, controlling for potential confounders. Results Relative to an annual household income of ≥$150,000, adjusted FRs were 0.91 (95% CI: 0.83-1.01) for Conclusions Lower levels of education and income were associated with modestly reduced Fecundability. These results demonstrate the presence of socioeconomic disparities in Fecundability.

  • glycemic load dietary fiber and added sugar and Fecundability in 2 preconception cohorts
    The American Journal of Clinical Nutrition, 2020
    Co-Authors: Sydney K Willis, Ellen M. Mikkelsen, Kenneth J. Rothman, Lauren A. Wise, Amelia K. Wesselink, Ellen Trolle, Katherine L Tucker, Elizabeth E. Hatch
    Abstract:

    Background Glycemic load (GL) reflects the quantity and quality of carbohydrates in the diet; dietary fiber and added sugar are components of GL. Few epidemiologic studies have assessed the association between these dietary factors and Fecundability. Objective We prospectively evaluated the associations of GL, total carbohydrates, dietary fiber, and added sugar with Fecundability. Methods Snart Foraeldre (SF) and Pregnancy Study Online (PRESTO) are parallel web-based prospective preconception cohorts of couples attempting to conceive in Denmark and North America. At baseline, female participants completed a web-based questionnaire on demographic and lifestyle factors and a validated FFQ. We calculated GL, total carbohydrate intake, total dietary fiber, carbohydrate-to-fiber ratio, and added sugar based on reported frequencies for individual foods, standard recipes for mixed foods, and average serving sizes. The analysis included 2709 SF participants and 4268 PRESTO participants. We used proportional probabilities regression models to estimate Fecundability ratios (FR) and 95% CIs. Results Compared with an average daily GL of ≤100, FRs for an average daily GL of ≥141 were 0.89 (95% CI: 0.73, 1.08) in SF and 0.87 (95% CI: 0.77, 0.98) in PRESTO participants. Compared with consuming ≤16 g/d of dietary fiber, FRs for consuming ≥25 g/d were 0.99 (95% CI: 0.81, 1.22) in SF and 1.06 (95% CI: 0.94, 1.20) in PRESTO. Compared with a carbohydrate-to-fiber ratio of ≤8, FRs for a ratio of ≥13 were 0.86 (95% CI: 0.73, 1.01) in SF and 0.87 (95% CI: 0.78, 0.98) in PRESTO. Compared with ≤27 g/d of added sugar, FRs for ≥72 g/d were 0.87 (95% CI: 0.68, 1.10) in SF and 0.86 (95% CI: 0.75, 0.99) in PRESTO participants. Conclusions Among women attempting to conceive in Denmark and North America, diets high in GL, carbohydrate-to-fiber ratio, and added sugar were associated with modestly reduced Fecundability.

Lauren A. Wise - One of the best experts on this subject based on the ideXlab platform.

  • association between male use of pain medication and Fecundability
    American Journal of Epidemiology, 2020
    Co-Authors: Amelia K. Wesselink, Ellen M. Mikkelsen, Kenneth J. Rothman, Elizabeth E. Hatch, Tanran R Wang, Kathryn A Bresnick, Krista F Huybrechts, Lauren A. Wise
    Abstract:

    Administration of pain relievers has been associated with both lower and higher risks of adverse reproductive outcomes in animals. In the sole investigation of male pain-reliever use and human fertility carried out to date, Smarr et al. (Hum Reprod. 2016;31(9):2119-2127) found a 35% reduction in Fecundability among males with urinary acetaminophen concentrations in the highest quartile (>73.5 ng/mL) versus the lowest (<5.4 ng/mL). We analyzed data from 1,956 males participating in Pregnancy Study Online, a preconception cohort study of North American couples enrolled between 2013 and 2019. Males and females completed baseline questionnaires on sociodemographic characteristics, lifestyle, medication use, and medical history; females completed bimonthly follow-up questionnaires for up to 12 months. We categorized pain medications by active ingredient (ibuprofen, acetaminophen, naproxen, aspirin) and cumulative monthly dose. We used proportional probabilities models to calculate Fecundability ratios and 95% confidence intervals, adjusting for potential confounders. In the 4 weeks before baseline, 51.7% of males used pain medications. Adjusted Fecundability ratios were 1.02 for ibuprofen (95% confidence interval (CI): 0.91, 1.13), 0.89 for acetaminophen (95% CI: 0.77, 1.03), 1.07 for naproxen (95% CI: 0.85, 1.35), and 1.05 for aspirin (95% CI: 0.81, 1.35), as compared with nonuse of each medication. In this study, male use of pain medications at low doses was not notably associated with Fecundability.

  • Fecundability in relation to use of mobile computing apps to track the menstrual cycle
    Human Reproduction, 2020
    Co-Authors: Joseph B Stanford, Kenneth J. Rothman, Elizabeth E. Hatch, Sydney K Willis, Lauren A. Wise
    Abstract:

    STUDY QUESTION To what extent does the use of mobile computing apps to track the menstrual cycle and the fertile window influence Fecundability among women trying to conceive? SUMMARY ANSWER After adjusting for potential confounders, use of any of several different apps was associated with increased Fecundability ranging from 12% to 20% per cycle of attempt. WHAT IS KNOWN ALREADY Many women are using mobile computing apps to track their menstrual cycle and the fertile window, including while trying to conceive. STUDY DESIGN, SIZE, DURATION The Pregnancy Study Online (PRESTO) is a North American prospective internet-based cohort of women who are aged 21-45 years, trying to conceive and not using contraception or fertility treatment at baseline. PARTICIPANTS/MATERIALS, SETTING, METHODS We restricted the analysis to 8363 women trying to conceive for no more than 6 months at baseline; the women were recruited from June 2013 through May 2019. Women completed questionnaires at baseline and every 2 months for up to 1 year. The main outcome was Fecundability, i.e. the per-cycle probability of conception, which we assessed using self-reported data on time to pregnancy (confirmed by positive home pregnancy test) in menstrual cycles. On the baseline and follow-up questionnaires, women reported whether they used mobile computing apps to track their menstrual cycles ('cycle apps') and, if so, which one(s). We estimated Fecundability ratios (FRs) for the use of cycle apps, adjusted for female age, race/ethnicity, prior pregnancy, BMI, income, current smoking, education, partner education, caffeine intake, use of hormonal contraceptives as the last method of contraception, hours of sleep per night, cycle regularity, use of prenatal supplements, marital status, intercourse frequency and history of subfertility. We also examined the impact of concurrent use of fertility indicators: basal body temperature, cervical fluid, cervix position and/or urine LH. MAIN RESULTS AND THE ROLE OF CHANCE Among 8363 women, 6077 (72.7%) were using one or more cycle apps at baseline. A total of 122 separate apps were reported by women. We designated five of these apps before analysis as more likely to be effective (Clue, Fertility Friend, Glow, Kindara, Ovia; hereafter referred to as 'selected apps'). The use of any app at baseline was associated with 20% increased Fecundability, with little difference between selected apps versus other apps (selected apps FR (95% CI): 1.20 (1.13, 1.28); all other apps 1.21 (1.13, 1.30)). In time-varying analyses, cycle app use was associated with 12-15% increased Fecundability (selected apps FR (95% CI): 1.12 (1.04, 1.21); all other apps 1.15 (1.07, 1.24)). When apps were used at baseline with one or more fertility indicators, there was higher Fecundability than without fertility indicators (selected apps with indicators FR (95% CI): 1.23 (1.14, 1.34) versus without indicators 1.17 (1.05, 1.30); other apps with indicators 1.30 (1.19, 1.43) versus without indicators 1.16 (1.06, 1.27)). In time-varying analyses, results were similar when stratified by time trying at study entry (<3 vs. 3-6 cycles) or cycle regularity. For use of the selected apps, we observed higher Fecundability among women with a history of subfertility: FR 1.33 (1.05-1.67). LIMITATIONS, REASONS FOR CAUTION Neither regularity nor intensity of app use was ascertained. The prospective time-varying assessment of app use was based on questionnaires completed every 2 months, which would not capture more frequent changes. Intercourse frequency was also reported retrospectively and we do not have data on timing of intercourse relative to the fertile window. Although we controlled for a wide range of covariates, we cannot exclude the possibility of residual confounding (e.g. choosing to use an app in this observational study may be a marker for unmeasured health habits promoting Fecundability). Half of the women in the study received a free premium subscription for one of the apps (Fertility Friend), which may have increased the overall prevalence of app use in the time-varying analyses, but would not affect app use at baseline. Most women in the study were college educated, which may limit application of results to other populations. WIDER IMPLICATIONS OF THE FINDINGS Use of a cycle app, especially in combination with observation of one or more fertility indicators (basal body temperature, cervical fluid, cervix position and/or urine LH), may increase Fecundability (per-cycle pregnancy probability) by about 12-20% for couples trying to conceive. We did not find consistent evidence of improved Fecundability resulting from use of one specific app over another. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by grants, R21HD072326 and R01HD086742, from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, USA. In the last 3 years, Dr L.A.W. has served as a fibroid consultant for AbbVie.com. Dr L.A.W. has also received in-kind donations from Sandstone Diagnostics, Swiss Precision Diagnostics, FertilityFriend.com and Kindara.com for primary data collection and participant incentives in the PRESTO cohort. Dr J.B.S. reports personal fees from Swiss Precision Diagnostics, outside the submitted work. The remaining authors have nothing to declare. TRIAL REGISTRATION NUMBER N/A.

  • association of income and education with Fecundability in a north american preconception cohort
    Annals of Epidemiology, 2020
    Co-Authors: Nina L Schrager, Ellen M. Mikkelsen, Kenneth J. Rothman, Elizabeth E. Hatch, Amelia K. Wesselink, Tanran R Wang, Renee Boyntonjarrett, Lauren A. Wise
    Abstract:

    Abstract Purpose To evaluate socioeconomic determinants of Fecundability. Methods Among 8,654 female pregnancy planners from Pregnancy Study Online, a North American prospective cohort study (2013-2019), we examined associations between socioeconomic status and Fecundability (the per-cycle probability of conception). Information on income and education was collected via baseline questionnaire. Bimonthly follow-up questionnaires were used to ascertain pregnancy status. We estimated Fecundability ratios (FRs) and 95% confidence intervals (CI) using proportional probabilities regression, controlling for potential confounders. Results Relative to an annual household income of ≥$150,000, adjusted FRs were 0.91 (95% CI: 0.83-1.01) for Conclusions Lower levels of education and income were associated with modestly reduced Fecundability. These results demonstrate the presence of socioeconomic disparities in Fecundability.

  • glycemic load dietary fiber and added sugar and Fecundability in 2 preconception cohorts
    The American Journal of Clinical Nutrition, 2020
    Co-Authors: Sydney K Willis, Ellen M. Mikkelsen, Kenneth J. Rothman, Lauren A. Wise, Amelia K. Wesselink, Ellen Trolle, Katherine L Tucker, Elizabeth E. Hatch
    Abstract:

    Background Glycemic load (GL) reflects the quantity and quality of carbohydrates in the diet; dietary fiber and added sugar are components of GL. Few epidemiologic studies have assessed the association between these dietary factors and Fecundability. Objective We prospectively evaluated the associations of GL, total carbohydrates, dietary fiber, and added sugar with Fecundability. Methods Snart Foraeldre (SF) and Pregnancy Study Online (PRESTO) are parallel web-based prospective preconception cohorts of couples attempting to conceive in Denmark and North America. At baseline, female participants completed a web-based questionnaire on demographic and lifestyle factors and a validated FFQ. We calculated GL, total carbohydrate intake, total dietary fiber, carbohydrate-to-fiber ratio, and added sugar based on reported frequencies for individual foods, standard recipes for mixed foods, and average serving sizes. The analysis included 2709 SF participants and 4268 PRESTO participants. We used proportional probabilities regression models to estimate Fecundability ratios (FR) and 95% CIs. Results Compared with an average daily GL of ≤100, FRs for an average daily GL of ≥141 were 0.89 (95% CI: 0.73, 1.08) in SF and 0.87 (95% CI: 0.77, 0.98) in PRESTO participants. Compared with consuming ≤16 g/d of dietary fiber, FRs for consuming ≥25 g/d were 0.99 (95% CI: 0.81, 1.22) in SF and 1.06 (95% CI: 0.94, 1.20) in PRESTO. Compared with a carbohydrate-to-fiber ratio of ≤8, FRs for a ratio of ≥13 were 0.86 (95% CI: 0.73, 1.01) in SF and 0.87 (95% CI: 0.78, 0.98) in PRESTO. Compared with ≤27 g/d of added sugar, FRs for ≥72 g/d were 0.87 (95% CI: 0.68, 1.10) in SF and 0.86 (95% CI: 0.75, 0.99) in PRESTO participants. Conclusions Among women attempting to conceive in Denmark and North America, diets high in GL, carbohydrate-to-fiber ratio, and added sugar were associated with modestly reduced Fecundability.

  • a prospective study of treatments for cervical intraepithelial neoplasia and Fecundability
    American Journal of Obstetrics and Gynecology, 2020
    Co-Authors: Lauren A. Wise, Ellen M. Mikkelsen, Amelia K. Wesselink, Kristen A Hahn, Sydney K Willis, Holly Michelle Crowe, Rebecca B Perkins, Alexandra M Klann, Elizabeth E. Hatch
    Abstract:

    Background Treatments for cervical intraepithelial neoplasia remove precancerous cells from the cervix by excising or ablating the transformation zone. Most studies show no association between cervical intraepithelial neoplasia treatments and fertility outcomes. However, only 2 studies have examined time to pregnancy, both using retrospective study designs, with 1 study showing no association and the other showing a 2-fold increased risk of infertility (time to pregnancy >12 months) following excisional or ablative treatment. Objective We examined the association between cervical intraepithelial neoplasia treatments and Fecundability. Materials and Methods We analyzed data from Pregnancy Study Online (PRESTO), a prospective cohort study of North American pregnancy planners enrolled during 2013−2019. At baseline, women reported whether they ever had an abnormal Papanicolaou test result, the number of abnormal Papanicolaou test results, and their age at first abnormal Papanicolaou test result. They also reported whether they underwent diagnostic (colposcopy) or treatment (excisional or ablative) procedures, and their age at each procedure. We restricted analyses to 8017 women with 6 or fewer cycles of attempt time at enrollment who reported receiving a Papanicolaou test in the previous 3 years. We estimated Fecundability ratios and 95% confidence intervals using proportional probabilities models adjusted for sociodemographics, healthcare use, smoking, number of sexual partners, history of sexually transmitted infections, and human papillomavirus vaccination. Results A history of abnormal Papanicolaou test results showed little association with Fecundability (Fecundability ratio, 1.00; 95% confidence interval, 0.95−1.06). Likewise, receipt of colposcopy or treatment procedures, and time since treatment were not materially associated with Fecundability. Results were similar when stratified by age and smoking status. Conclusion We observed no appreciable association of self-reported history of abnormal Papanicolaou test results, colposcopy, treatments for cervical intraepithelial neoplasia, or recency of treatment with Fecundability. These results agree with the majority of previous studies in indicating little effect of cervical intraepithelial neoplasia treatments on future fertility.

Elizabeth E. Hatch - One of the best experts on this subject based on the ideXlab platform.

  • pregravid contraceptive use and Fecundability prospective cohort study
    BMJ, 2020
    Co-Authors: Jennifer J Yland, Ellen M. Mikkelsen, Kenneth J. Rothman, Elizabeth E. Hatch, Henrik Toft Sørensen, Amelia K. Wesselink, Kathryn A Bresnick, Krista F Huybrechts
    Abstract:

    Abstract Objective To evaluate the association between pregravid use of a variety of contraceptive methods and subsequent Fecundability. Design Prospective cohort study. Setting Denmark and North America, 2007-19. Participants 17 954 women who had tried to conceive for up to six menstrual cycles at study entry. At baseline, participants reported their contraceptive histories, and personal, medical, and lifestyle characteristics. Main outcome measures Pregnancy, determined by bimonthly follow-up questionnaires for up to 12 months. Results Approximately 38% (n=6735) of participants had recently used oral contraceptives, 13% (n=2398) had used long acting reversible contraceptive methods, and 31% (n=5497) had used barrier methods. Women who had recently stopped using oral contraceptives, the contraceptive ring, and some long acting reversible contraceptive methods experienced short term delays in return of fertility compared with users of barrier methods. Use of injectable contraceptives was associated with decreased Fecundability compared with use of barrier methods (Fecundability ratio 0.65; 95% confidence interval 0.47 to 0.89). Users of injectable contraceptives had the longest delay in return of normal fertility (five to eight menstrual cycles), followed by users of patch contraceptives (four cycles), users of oral and ring contraceptives (three cycles), and users of hormonal and copper intrauterine devices and implant contraceptives (two cycles). Lifetime length of use of hormonal contraceptive methods was not associated with Fecundability. Conclusions Use of some hormonal contraceptive methods was associated with delays in return of fertility, with injectable contraceptives showing the longest delay. The findings indicated little or no lasting effect of long term use of these methods on Fecundability.

  • association between male use of pain medication and Fecundability
    American Journal of Epidemiology, 2020
    Co-Authors: Amelia K. Wesselink, Ellen M. Mikkelsen, Kenneth J. Rothman, Elizabeth E. Hatch, Tanran R Wang, Kathryn A Bresnick, Krista F Huybrechts, Lauren A. Wise
    Abstract:

    Administration of pain relievers has been associated with both lower and higher risks of adverse reproductive outcomes in animals. In the sole investigation of male pain-reliever use and human fertility carried out to date, Smarr et al. (Hum Reprod. 2016;31(9):2119-2127) found a 35% reduction in Fecundability among males with urinary acetaminophen concentrations in the highest quartile (>73.5 ng/mL) versus the lowest (<5.4 ng/mL). We analyzed data from 1,956 males participating in Pregnancy Study Online, a preconception cohort study of North American couples enrolled between 2013 and 2019. Males and females completed baseline questionnaires on sociodemographic characteristics, lifestyle, medication use, and medical history; females completed bimonthly follow-up questionnaires for up to 12 months. We categorized pain medications by active ingredient (ibuprofen, acetaminophen, naproxen, aspirin) and cumulative monthly dose. We used proportional probabilities models to calculate Fecundability ratios and 95% confidence intervals, adjusting for potential confounders. In the 4 weeks before baseline, 51.7% of males used pain medications. Adjusted Fecundability ratios were 1.02 for ibuprofen (95% confidence interval (CI): 0.91, 1.13), 0.89 for acetaminophen (95% CI: 0.77, 1.03), 1.07 for naproxen (95% CI: 0.85, 1.35), and 1.05 for aspirin (95% CI: 0.81, 1.35), as compared with nonuse of each medication. In this study, male use of pain medications at low doses was not notably associated with Fecundability.

  • Fecundability in relation to use of mobile computing apps to track the menstrual cycle
    Human Reproduction, 2020
    Co-Authors: Joseph B Stanford, Kenneth J. Rothman, Elizabeth E. Hatch, Sydney K Willis, Lauren A. Wise
    Abstract:

    STUDY QUESTION To what extent does the use of mobile computing apps to track the menstrual cycle and the fertile window influence Fecundability among women trying to conceive? SUMMARY ANSWER After adjusting for potential confounders, use of any of several different apps was associated with increased Fecundability ranging from 12% to 20% per cycle of attempt. WHAT IS KNOWN ALREADY Many women are using mobile computing apps to track their menstrual cycle and the fertile window, including while trying to conceive. STUDY DESIGN, SIZE, DURATION The Pregnancy Study Online (PRESTO) is a North American prospective internet-based cohort of women who are aged 21-45 years, trying to conceive and not using contraception or fertility treatment at baseline. PARTICIPANTS/MATERIALS, SETTING, METHODS We restricted the analysis to 8363 women trying to conceive for no more than 6 months at baseline; the women were recruited from June 2013 through May 2019. Women completed questionnaires at baseline and every 2 months for up to 1 year. The main outcome was Fecundability, i.e. the per-cycle probability of conception, which we assessed using self-reported data on time to pregnancy (confirmed by positive home pregnancy test) in menstrual cycles. On the baseline and follow-up questionnaires, women reported whether they used mobile computing apps to track their menstrual cycles ('cycle apps') and, if so, which one(s). We estimated Fecundability ratios (FRs) for the use of cycle apps, adjusted for female age, race/ethnicity, prior pregnancy, BMI, income, current smoking, education, partner education, caffeine intake, use of hormonal contraceptives as the last method of contraception, hours of sleep per night, cycle regularity, use of prenatal supplements, marital status, intercourse frequency and history of subfertility. We also examined the impact of concurrent use of fertility indicators: basal body temperature, cervical fluid, cervix position and/or urine LH. MAIN RESULTS AND THE ROLE OF CHANCE Among 8363 women, 6077 (72.7%) were using one or more cycle apps at baseline. A total of 122 separate apps were reported by women. We designated five of these apps before analysis as more likely to be effective (Clue, Fertility Friend, Glow, Kindara, Ovia; hereafter referred to as 'selected apps'). The use of any app at baseline was associated with 20% increased Fecundability, with little difference between selected apps versus other apps (selected apps FR (95% CI): 1.20 (1.13, 1.28); all other apps 1.21 (1.13, 1.30)). In time-varying analyses, cycle app use was associated with 12-15% increased Fecundability (selected apps FR (95% CI): 1.12 (1.04, 1.21); all other apps 1.15 (1.07, 1.24)). When apps were used at baseline with one or more fertility indicators, there was higher Fecundability than without fertility indicators (selected apps with indicators FR (95% CI): 1.23 (1.14, 1.34) versus without indicators 1.17 (1.05, 1.30); other apps with indicators 1.30 (1.19, 1.43) versus without indicators 1.16 (1.06, 1.27)). In time-varying analyses, results were similar when stratified by time trying at study entry (<3 vs. 3-6 cycles) or cycle regularity. For use of the selected apps, we observed higher Fecundability among women with a history of subfertility: FR 1.33 (1.05-1.67). LIMITATIONS, REASONS FOR CAUTION Neither regularity nor intensity of app use was ascertained. The prospective time-varying assessment of app use was based on questionnaires completed every 2 months, which would not capture more frequent changes. Intercourse frequency was also reported retrospectively and we do not have data on timing of intercourse relative to the fertile window. Although we controlled for a wide range of covariates, we cannot exclude the possibility of residual confounding (e.g. choosing to use an app in this observational study may be a marker for unmeasured health habits promoting Fecundability). Half of the women in the study received a free premium subscription for one of the apps (Fertility Friend), which may have increased the overall prevalence of app use in the time-varying analyses, but would not affect app use at baseline. Most women in the study were college educated, which may limit application of results to other populations. WIDER IMPLICATIONS OF THE FINDINGS Use of a cycle app, especially in combination with observation of one or more fertility indicators (basal body temperature, cervical fluid, cervix position and/or urine LH), may increase Fecundability (per-cycle pregnancy probability) by about 12-20% for couples trying to conceive. We did not find consistent evidence of improved Fecundability resulting from use of one specific app over another. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by grants, R21HD072326 and R01HD086742, from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, USA. In the last 3 years, Dr L.A.W. has served as a fibroid consultant for AbbVie.com. Dr L.A.W. has also received in-kind donations from Sandstone Diagnostics, Swiss Precision Diagnostics, FertilityFriend.com and Kindara.com for primary data collection and participant incentives in the PRESTO cohort. Dr J.B.S. reports personal fees from Swiss Precision Diagnostics, outside the submitted work. The remaining authors have nothing to declare. TRIAL REGISTRATION NUMBER N/A.

  • association of income and education with Fecundability in a north american preconception cohort
    Annals of Epidemiology, 2020
    Co-Authors: Nina L Schrager, Ellen M. Mikkelsen, Kenneth J. Rothman, Elizabeth E. Hatch, Amelia K. Wesselink, Tanran R Wang, Renee Boyntonjarrett, Lauren A. Wise
    Abstract:

    Abstract Purpose To evaluate socioeconomic determinants of Fecundability. Methods Among 8,654 female pregnancy planners from Pregnancy Study Online, a North American prospective cohort study (2013-2019), we examined associations between socioeconomic status and Fecundability (the per-cycle probability of conception). Information on income and education was collected via baseline questionnaire. Bimonthly follow-up questionnaires were used to ascertain pregnancy status. We estimated Fecundability ratios (FRs) and 95% confidence intervals (CI) using proportional probabilities regression, controlling for potential confounders. Results Relative to an annual household income of ≥$150,000, adjusted FRs were 0.91 (95% CI: 0.83-1.01) for Conclusions Lower levels of education and income were associated with modestly reduced Fecundability. These results demonstrate the presence of socioeconomic disparities in Fecundability.

  • glycemic load dietary fiber and added sugar and Fecundability in 2 preconception cohorts
    The American Journal of Clinical Nutrition, 2020
    Co-Authors: Sydney K Willis, Ellen M. Mikkelsen, Kenneth J. Rothman, Lauren A. Wise, Amelia K. Wesselink, Ellen Trolle, Katherine L Tucker, Elizabeth E. Hatch
    Abstract:

    Background Glycemic load (GL) reflects the quantity and quality of carbohydrates in the diet; dietary fiber and added sugar are components of GL. Few epidemiologic studies have assessed the association between these dietary factors and Fecundability. Objective We prospectively evaluated the associations of GL, total carbohydrates, dietary fiber, and added sugar with Fecundability. Methods Snart Foraeldre (SF) and Pregnancy Study Online (PRESTO) are parallel web-based prospective preconception cohorts of couples attempting to conceive in Denmark and North America. At baseline, female participants completed a web-based questionnaire on demographic and lifestyle factors and a validated FFQ. We calculated GL, total carbohydrate intake, total dietary fiber, carbohydrate-to-fiber ratio, and added sugar based on reported frequencies for individual foods, standard recipes for mixed foods, and average serving sizes. The analysis included 2709 SF participants and 4268 PRESTO participants. We used proportional probabilities regression models to estimate Fecundability ratios (FR) and 95% CIs. Results Compared with an average daily GL of ≤100, FRs for an average daily GL of ≥141 were 0.89 (95% CI: 0.73, 1.08) in SF and 0.87 (95% CI: 0.77, 0.98) in PRESTO participants. Compared with consuming ≤16 g/d of dietary fiber, FRs for consuming ≥25 g/d were 0.99 (95% CI: 0.81, 1.22) in SF and 1.06 (95% CI: 0.94, 1.20) in PRESTO. Compared with a carbohydrate-to-fiber ratio of ≤8, FRs for a ratio of ≥13 were 0.86 (95% CI: 0.73, 1.01) in SF and 0.87 (95% CI: 0.78, 0.98) in PRESTO. Compared with ≤27 g/d of added sugar, FRs for ≥72 g/d were 0.87 (95% CI: 0.68, 1.10) in SF and 0.86 (95% CI: 0.75, 0.99) in PRESTO participants. Conclusions Among women attempting to conceive in Denmark and North America, diets high in GL, carbohydrate-to-fiber ratio, and added sugar were associated with modestly reduced Fecundability.

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  • pregravid contraceptive use and Fecundability prospective cohort study
    BMJ, 2020
    Co-Authors: Jennifer J Yland, Ellen M. Mikkelsen, Kenneth J. Rothman, Elizabeth E. Hatch, Henrik Toft Sørensen, Amelia K. Wesselink, Kathryn A Bresnick, Krista F Huybrechts
    Abstract:

    Abstract Objective To evaluate the association between pregravid use of a variety of contraceptive methods and subsequent Fecundability. Design Prospective cohort study. Setting Denmark and North America, 2007-19. Participants 17 954 women who had tried to conceive for up to six menstrual cycles at study entry. At baseline, participants reported their contraceptive histories, and personal, medical, and lifestyle characteristics. Main outcome measures Pregnancy, determined by bimonthly follow-up questionnaires for up to 12 months. Results Approximately 38% (n=6735) of participants had recently used oral contraceptives, 13% (n=2398) had used long acting reversible contraceptive methods, and 31% (n=5497) had used barrier methods. Women who had recently stopped using oral contraceptives, the contraceptive ring, and some long acting reversible contraceptive methods experienced short term delays in return of fertility compared with users of barrier methods. Use of injectable contraceptives was associated with decreased Fecundability compared with use of barrier methods (Fecundability ratio 0.65; 95% confidence interval 0.47 to 0.89). Users of injectable contraceptives had the longest delay in return of normal fertility (five to eight menstrual cycles), followed by users of patch contraceptives (four cycles), users of oral and ring contraceptives (three cycles), and users of hormonal and copper intrauterine devices and implant contraceptives (two cycles). Lifetime length of use of hormonal contraceptive methods was not associated with Fecundability. Conclusions Use of some hormonal contraceptive methods was associated with delays in return of fertility, with injectable contraceptives showing the longest delay. The findings indicated little or no lasting effect of long term use of these methods on Fecundability.

  • association between male use of pain medication and Fecundability
    American Journal of Epidemiology, 2020
    Co-Authors: Amelia K. Wesselink, Ellen M. Mikkelsen, Kenneth J. Rothman, Elizabeth E. Hatch, Tanran R Wang, Kathryn A Bresnick, Krista F Huybrechts, Lauren A. Wise
    Abstract:

    Administration of pain relievers has been associated with both lower and higher risks of adverse reproductive outcomes in animals. In the sole investigation of male pain-reliever use and human fertility carried out to date, Smarr et al. (Hum Reprod. 2016;31(9):2119-2127) found a 35% reduction in Fecundability among males with urinary acetaminophen concentrations in the highest quartile (>73.5 ng/mL) versus the lowest (<5.4 ng/mL). We analyzed data from 1,956 males participating in Pregnancy Study Online, a preconception cohort study of North American couples enrolled between 2013 and 2019. Males and females completed baseline questionnaires on sociodemographic characteristics, lifestyle, medication use, and medical history; females completed bimonthly follow-up questionnaires for up to 12 months. We categorized pain medications by active ingredient (ibuprofen, acetaminophen, naproxen, aspirin) and cumulative monthly dose. We used proportional probabilities models to calculate Fecundability ratios and 95% confidence intervals, adjusting for potential confounders. In the 4 weeks before baseline, 51.7% of males used pain medications. Adjusted Fecundability ratios were 1.02 for ibuprofen (95% confidence interval (CI): 0.91, 1.13), 0.89 for acetaminophen (95% CI: 0.77, 1.03), 1.07 for naproxen (95% CI: 0.85, 1.35), and 1.05 for aspirin (95% CI: 0.81, 1.35), as compared with nonuse of each medication. In this study, male use of pain medications at low doses was not notably associated with Fecundability.

  • association of income and education with Fecundability in a north american preconception cohort
    Annals of Epidemiology, 2020
    Co-Authors: Nina L Schrager, Ellen M. Mikkelsen, Kenneth J. Rothman, Elizabeth E. Hatch, Amelia K. Wesselink, Tanran R Wang, Renee Boyntonjarrett, Lauren A. Wise
    Abstract:

    Abstract Purpose To evaluate socioeconomic determinants of Fecundability. Methods Among 8,654 female pregnancy planners from Pregnancy Study Online, a North American prospective cohort study (2013-2019), we examined associations between socioeconomic status and Fecundability (the per-cycle probability of conception). Information on income and education was collected via baseline questionnaire. Bimonthly follow-up questionnaires were used to ascertain pregnancy status. We estimated Fecundability ratios (FRs) and 95% confidence intervals (CI) using proportional probabilities regression, controlling for potential confounders. Results Relative to an annual household income of ≥$150,000, adjusted FRs were 0.91 (95% CI: 0.83-1.01) for Conclusions Lower levels of education and income were associated with modestly reduced Fecundability. These results demonstrate the presence of socioeconomic disparities in Fecundability.

  • glycemic load dietary fiber and added sugar and Fecundability in 2 preconception cohorts
    The American Journal of Clinical Nutrition, 2020
    Co-Authors: Sydney K Willis, Ellen M. Mikkelsen, Kenneth J. Rothman, Lauren A. Wise, Amelia K. Wesselink, Ellen Trolle, Katherine L Tucker, Elizabeth E. Hatch
    Abstract:

    Background Glycemic load (GL) reflects the quantity and quality of carbohydrates in the diet; dietary fiber and added sugar are components of GL. Few epidemiologic studies have assessed the association between these dietary factors and Fecundability. Objective We prospectively evaluated the associations of GL, total carbohydrates, dietary fiber, and added sugar with Fecundability. Methods Snart Foraeldre (SF) and Pregnancy Study Online (PRESTO) are parallel web-based prospective preconception cohorts of couples attempting to conceive in Denmark and North America. At baseline, female participants completed a web-based questionnaire on demographic and lifestyle factors and a validated FFQ. We calculated GL, total carbohydrate intake, total dietary fiber, carbohydrate-to-fiber ratio, and added sugar based on reported frequencies for individual foods, standard recipes for mixed foods, and average serving sizes. The analysis included 2709 SF participants and 4268 PRESTO participants. We used proportional probabilities regression models to estimate Fecundability ratios (FR) and 95% CIs. Results Compared with an average daily GL of ≤100, FRs for an average daily GL of ≥141 were 0.89 (95% CI: 0.73, 1.08) in SF and 0.87 (95% CI: 0.77, 0.98) in PRESTO participants. Compared with consuming ≤16 g/d of dietary fiber, FRs for consuming ≥25 g/d were 0.99 (95% CI: 0.81, 1.22) in SF and 1.06 (95% CI: 0.94, 1.20) in PRESTO. Compared with a carbohydrate-to-fiber ratio of ≤8, FRs for a ratio of ≥13 were 0.86 (95% CI: 0.73, 1.01) in SF and 0.87 (95% CI: 0.78, 0.98) in PRESTO. Compared with ≤27 g/d of added sugar, FRs for ≥72 g/d were 0.87 (95% CI: 0.68, 1.10) in SF and 0.86 (95% CI: 0.75, 0.99) in PRESTO participants. Conclusions Among women attempting to conceive in Denmark and North America, diets high in GL, carbohydrate-to-fiber ratio, and added sugar were associated with modestly reduced Fecundability.

  • a prospective study of treatments for cervical intraepithelial neoplasia and Fecundability
    American Journal of Obstetrics and Gynecology, 2020
    Co-Authors: Lauren A. Wise, Ellen M. Mikkelsen, Amelia K. Wesselink, Kristen A Hahn, Sydney K Willis, Holly Michelle Crowe, Rebecca B Perkins, Alexandra M Klann, Elizabeth E. Hatch
    Abstract:

    Background Treatments for cervical intraepithelial neoplasia remove precancerous cells from the cervix by excising or ablating the transformation zone. Most studies show no association between cervical intraepithelial neoplasia treatments and fertility outcomes. However, only 2 studies have examined time to pregnancy, both using retrospective study designs, with 1 study showing no association and the other showing a 2-fold increased risk of infertility (time to pregnancy >12 months) following excisional or ablative treatment. Objective We examined the association between cervical intraepithelial neoplasia treatments and Fecundability. Materials and Methods We analyzed data from Pregnancy Study Online (PRESTO), a prospective cohort study of North American pregnancy planners enrolled during 2013−2019. At baseline, women reported whether they ever had an abnormal Papanicolaou test result, the number of abnormal Papanicolaou test results, and their age at first abnormal Papanicolaou test result. They also reported whether they underwent diagnostic (colposcopy) or treatment (excisional or ablative) procedures, and their age at each procedure. We restricted analyses to 8017 women with 6 or fewer cycles of attempt time at enrollment who reported receiving a Papanicolaou test in the previous 3 years. We estimated Fecundability ratios and 95% confidence intervals using proportional probabilities models adjusted for sociodemographics, healthcare use, smoking, number of sexual partners, history of sexually transmitted infections, and human papillomavirus vaccination. Results A history of abnormal Papanicolaou test results showed little association with Fecundability (Fecundability ratio, 1.00; 95% confidence interval, 0.95−1.06). Likewise, receipt of colposcopy or treatment procedures, and time since treatment were not materially associated with Fecundability. Results were similar when stratified by age and smoking status. Conclusion We observed no appreciable association of self-reported history of abnormal Papanicolaou test results, colposcopy, treatments for cervical intraepithelial neoplasia, or recency of treatment with Fecundability. These results agree with the majority of previous studies in indicating little effect of cervical intraepithelial neoplasia treatments on future fertility.

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  • pregravid contraceptive use and Fecundability prospective cohort study
    BMJ, 2020
    Co-Authors: Jennifer J Yland, Ellen M. Mikkelsen, Kenneth J. Rothman, Elizabeth E. Hatch, Henrik Toft Sørensen, Amelia K. Wesselink, Kathryn A Bresnick, Krista F Huybrechts
    Abstract:

    Abstract Objective To evaluate the association between pregravid use of a variety of contraceptive methods and subsequent Fecundability. Design Prospective cohort study. Setting Denmark and North America, 2007-19. Participants 17 954 women who had tried to conceive for up to six menstrual cycles at study entry. At baseline, participants reported their contraceptive histories, and personal, medical, and lifestyle characteristics. Main outcome measures Pregnancy, determined by bimonthly follow-up questionnaires for up to 12 months. Results Approximately 38% (n=6735) of participants had recently used oral contraceptives, 13% (n=2398) had used long acting reversible contraceptive methods, and 31% (n=5497) had used barrier methods. Women who had recently stopped using oral contraceptives, the contraceptive ring, and some long acting reversible contraceptive methods experienced short term delays in return of fertility compared with users of barrier methods. Use of injectable contraceptives was associated with decreased Fecundability compared with use of barrier methods (Fecundability ratio 0.65; 95% confidence interval 0.47 to 0.89). Users of injectable contraceptives had the longest delay in return of normal fertility (five to eight menstrual cycles), followed by users of patch contraceptives (four cycles), users of oral and ring contraceptives (three cycles), and users of hormonal and copper intrauterine devices and implant contraceptives (two cycles). Lifetime length of use of hormonal contraceptive methods was not associated with Fecundability. Conclusions Use of some hormonal contraceptive methods was associated with delays in return of fertility, with injectable contraceptives showing the longest delay. The findings indicated little or no lasting effect of long term use of these methods on Fecundability.

  • association of asthma diagnosis and medication use with Fecundability a prospective cohort study
    Clinical Epidemiology, 2020
    Co-Authors: Holly Michelle Crowe, Ellen M. Mikkelsen, Kenneth J. Rothman, Henrik Toft Sørensen, Lauren A. Wise, Amelia K. Wesselink, Allan J Walkey, Elizabeth E. Hatch
    Abstract:

    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.

  • seasonal patterns in Fecundability in north america and denmark a preconception cohort study
    Human Reproduction, 2020
    Co-Authors: Amelia K. Wesselink, Ellen M. Mikkelsen, Kenneth J. Rothman, Elizabeth E. Hatch, Henrik Toft Sørensen, Anders H. Riis, Lauren A. Wise, Craig J Mckinnon
    Abstract:

    Study question To what extent does Fecundability vary across seasons? Summary answer After accounting for seasonal patterns in pregnancy planning, we observed higher Fecundability in the fall and lower Fecundability in the spring, particularly at lower latitudes. What is known already In human populations, there are strong seasonal patterns of births that vary across geographic regions and time periods. However, previous studies of seasonality and fecundity are limited because they examine season of birth rather than season of conception and therefore neglect to account for seasonal variation in initiating attempts to conceive or pregnancy loss or differences in gestational length. Study design, size, duration We conducted a preconception cohort study of 14 331 women residing in North America (June 2013-May 2018: n = 5827) and Denmark (June 2007-May 2018: n = 8504). Participants were attempting to conceive without fertility treatment and had been attempting pregnancy for ≤6 menstrual cycles at enrolment. Participants/material, setting, methods We collected information on season of each pregnancy attempt using last menstrual period dates over the study period. Pregnancy was reported on female bi-monthly follow-up questionnaires. We fit log-binomial models with trigonometric regression to examine periodic variation in Fecundability. We accounted for seasonal variation in initiation of pregnancy attempts by including indicator variables for menstrual cycle of attempt in the regression models. Main results and the role of chance Initiation of pregnancy attempts peaked in September, with stronger seasonality in North America than in Denmark (48 vs. 16% higher probability initiating attempts in September compared with March). After accounting for seasonal variation in initiation of pregnancy attempts, we observed modest seasonal variation in Fecundability, with a peak in the late fall and early winter in both cohorts, but stronger peak/low ratios in North America (1.16; 95% confidence interval [CI]: 1.05, 1.28) than in Denmark (1.08; 95% CI: 1.00, 1.16). When we stratified the North American data by latitude, we observed the strongest seasonal variation in the southern USA (peak/low ratio of 1.45 [95% CI: 1.14, 1.84]), with peak Fecundability in late November. Limitations, reasons for caution We estimated menstrual cycle dates between follow-up questionnaires, which may have introduced exposure misclassification, particularly when women skipped follow-up questionnaires. We were unable to measure seasonally varying factors that may have influenced Fecundability, including ambient temperature, vitamin D levels or infectious disease. Wider implications of the findings An understanding of how Fecundability varies across seasons could help identify factors that can impair reproductive function. Neglecting to account for seasonal variation in initiation of pregnancy attempts could bias estimates of seasonal patterns in Fecundability. This is the first preconception cohort study to examine seasonal variation in Fecundability after accounting for seasonality in initiation of pregnancy attempts. Fecundability was highest in the fall and lowest in the spring, with stronger effects in southern latitudes of North America, suggesting that seasonal exposures may affect fecundity. Study funding/competing interest(s) This research was funded by the Eunice K. Shriver National Institute of Child Health and Human Development (R21-050264, R01-HD060680, R21-HD072326 and R01-HD086742) and the Danish Medical Research Council (271-07-0338). The authors declare no conflicts of interest.

  • iron consumption is not consistently associated with Fecundability among north american and danish pregnancy planners
    Journal of Nutrition, 2019
    Co-Authors: Kristen A Hahn, Ellen M. Mikkelsen, Kenneth J. Rothman, Lauren A. Wise, Amelia K. Wesselink, Katherine L Tucker, Heidi T Cueto, Marco Vinceti, Henrik Toft Sørensen
    Abstract:

    BACKGROUND Infertility is an important public health problem with few known modifiable risk factors. Dietary factors including folic acid have been associated with improved fertility, but the association between iron and fertility is understudied. One study among US nurses found a 40% lower risk of ovulatory infertility with higher intake of nonheme iron and iron supplements. OBJECTIVES The aim of this study was to determine the extent to which iron intake from diet and supplements reported on structured questionnaires is associated with Fecundability. METHODS We conducted parallel analyses that used data from 2 prospective cohort studies of pregnancy planners from Denmark (Snart Foraeldre; n = 1693) and North America (PRESTO; n = 2969) during 2013-2018. Follow-up comprised menstrual cycles at risk until pregnancy or censoring for fertility treatment, stopped trying to conceive, withdrawal, loss to follow-up, or 12 cycles of attempt. We used proportional probabilities regression models to estimate Fecundability ratios (FRs) and 95% CIs, adjusting for confounders. RESULTS We found little association between dietary heme iron intake and Fecundability in either cohort. The FR for nonheme iron intake (≥11 mg/d compared with <9 mg/day) was 1.11 for Snart Foraeldre participants (95% CI: 0.92, 1.34) and 1.01 for PRESTO participants (95% CI: 0.89, 1.14). The FR for iron-containing supplements was 1.01 in Snart Foraeldre (95% CI: 0.90, 1.13) and 1.19 in PRESTO (95% CI: 1.03, 1.38). In PRESTO, but not Snart Foraeldre, stronger positive associations were found for nonheme iron intake and iron supplement use among women with heavy menses or short menstrual cycles. CONCLUSIONS Overall, dietary intake of iron was not consistently associated with Fecundability, although there was some evidence for a positive association among women with risk factors for iron deficiency. We also found a small positive association between supplemental iron intake and Fecundability among North American, but not Danish, pregnancy planners.

  • Fecundability among danish women with a history of miscarriage a prospective cohort study
    BMJ Open, 2019
    Co-Authors: Cathrine Wildenschild, Kenneth J. Rothman, Elizabeth E. Hatch, Henrik Toft Sørensen, Anders H. Riis, Lauren A. Wise, Vera Ehrenstein, Ellen M. Mikkelsen
    Abstract:

    Objective To examine the association between history of miscarriage and Fecundability (the cycle-specific probability of conception). Design Nationwide prospective cohort study using web-based questionnaires. Setting Denmark, 2007–2012. Participants 977 women attempting to conceive, not using fertility treatment, and with a reproductive history of only miscarriage or only live birth. Exposure and outcome measures Information on previous pregnancy outcomes, including miscarriage, came from self-report or from relevant registries. Participants were followed for up to 12 months or until they reported a pregnancy, stopped trying to conceive or started fertility treatment, whichever came first. We used Kaplan-Meier methods to estimate cumulative probabilities of conception for women whose reproductive history included only miscarriage or only live birth. Using proportional probabilities regression modelling, we computed Fecundability ratios (FR) with 95% CI comparing women with a history of only miscarriage with women with a history of only live birth. Results After adjustment for potential confounders, the cumulative probabilities of conception within 12 cycles of follow-up were 85% (95% CI 81% to 89%) for women with a history of 1 miscarriage, 85% (95% CI 73% to 92%) for women with a history of ≥2 miscarriages and 88% (95% CI 87% to 89%) for women whose reproductive history included only live birth. Adjusted FRs were 0.87 (95% CI 0.71 to 1.07) and 0.65 (95% CI 0.36 to 1.17) for women with a history of 1 and ≥2 miscarriages, respectively. Conclusions Our results indicate that women with a history of miscarriage may have slightly reduced Fecundability compared with women with a history of only live birth. The reduction in Fecundability was greater for women with repeated miscarriages, although the estimates were imprecise. Despite a potential delay in conception, women with previous miscarriage may have similar probability of pregnancy by 12 cycles of attempts to women with proven fertility.