ABSTRACT Background Epidemiologic studies have demonstrated that ambient concentrations of particulate matter < 2.5 μm (PM 2.5 ) are associated with reduced fecundability, the per cycle probability of conception. The specific constituents driving this association are unknown. Objectives We examined the association between ambient concentrations of PM 2.5 constituents and fecundability in a Danish preconception cohort study. Methods During 2007–2018, we enrolled female pregnancy planners in an Internet‐based preconception cohort study. We included the 5905 participants who had been trying to conceive for < 3 cycles at study enrollment. Participants completed a baseline questionnaire and follow‐up questionnaires every 8 weeks to update pregnancy status. We geocoded time‐varying residential addresses to estimate ambient concentrations of total PM 2.5 and the following PM 2.5 constituents: elemental carbon (EC), primary organic aerosol (POA), secondary organic aerosols (SOA), sulfate (SO 4 2− ), ammonium (NH 4 + ), nitrate (NO 3 − ), and sea salt. We averaged concentrations of each pollutant across each menstrual cycle at risk. We fit proportional probabilities regression models to estimate fecundability ratios (FR) and 95% confidence intervals (CI), adjusting for potential confounders and co‐pollutants. Results Total PM 2.5 concentrations were associated with reduced fecundability (the FR for an IQR increase, corresponding to 3.2 μg/m 3 , was 0.93 [95% CI 0.87, 0.99]). The association was strongest for POA: the FR for an IQR increase, corresponding to 1.3 μg/m 3 , was 0.92 (95% CI 0.84, 1.01). The corresponding FRs for the remaining PM 2.5 constituents were 0.96 (95% CI 0.87, 1.05) for EC (IQR = 0.5 μg/m 3 ), 0.98 (95% CI 0.91, 1.06) for SOA (IQR = 0.5), 0.97 (95% CI 0.92, 1.02) for SO 2 4− (IQR = 0.4), 0.95 (95% CI 0.91, 1.01) for NH 4 + (IQR = 0.5), 0.97 (95% CI 0.93, 1.01) for NO 3 − (IQR = 1.0), and 1.00 (95% CI 0.95, 1.06) for sea salt (IQR = 0.4). Conclusions In this Danish preconception cohort study, PM 2.5 constituents derived from biomass and transportation‐related combustion may drive the association between PM 2.5 concentrations and fecundability.

STUDY QUESTION:To what extent is male physical activity (PA) associated with fecundability (per-cycle probability of conception)? SUMMARY ANSWER:Preconception levels of vigorous, moderate, or total PA were not consistently associated with fecundability across Danish and North American cohorts, but there was suggestive evidence that bicycling with a 'soft, comfort seat' was associated with reduced fecundability in both cohorts, especially among males with greater BMI. WHAT IS KNOWN ALREADY:Among males, some studies indicate that moderate PA might improve fertility, whereas vigorous PA, especially bicycling, might be detrimental. STUDY DESIGN, SIZE, DURATION:We assessed the association between male PA and fecundability among couples participating in two preconception cohort studies: SnartForaeldre.dk (SF) in Denmark (2011-2023) and Pregnancy Study Online (PRESTO) in North America (2013-2024). We restricted analyses to 4921 males (1088 in SF and 3833 in PRESTO) who had been trying to conceive with their partners for ≤6 cycles at enrollment. PARTICIPANTS/MATERIALS, SETTING, METHODS:At baseline, male partners reported data on medical history, lifestyle, behavioral, anthropometric factors, and their PA levels using different instruments [SF: International Physical Activity Questionnaire (IPAQ); PRESTO: average annual hours/week and type]. Both cohorts included additional questions on bicycling (frequency, bike seat type). After linking couple data at baseline, the female partner completed follow-up questionnaires to update their pregnancy status every 8 weeks for 12 months or until conception, whichever occurred first. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs, controlling for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE:Average hours/week of vigorous PA, moderate PA, and total metabolic equivalents of task were generally inversely associated with fecundability in SF, but not PRESTO. While there was little association with bicycling overall in either cohort, we observed an inverse association for bicycling using a 'soft, comfort seat' (≥3 vs 0 h/week: SF: FR = 0.75, 95% CI: 0.53-1.05; PRESTO: FR = 0.81, 95% CI: 0.62-1.07) but not a 'hard, racing-style seat' (≥3 vs 0 h/week: SF: FR = 1.16, 95% CI: 0.95-1.41; PRESTO: FR = 1.06, 95% CI: 0.89-1.28). Among males with BMI ≥25 kg/m2, associations with bicycling using a 'soft, comfort seat' were similar or stronger (≥3 vs 0 h/week: SF: FR = 0.75, 95% CI: 0.45-1.24; PRESTO: FR = 0.73, 95% CI: 0.52-1.03). LIMITATIONS, REASONS FOR CAUTION:Misclassification of PA was likely the most important study limitation because we ascertained PA only once at enrollment using different instruments in each cohort. We would expect misclassification of PA to be non-differential given the prospective study design. Additional weaknesses include the narrow range of PA levels evaluated, reduced precision when stratifying the data by selected covariates, and limited generalizability due to the large percentage of non-Hispanic White participants and restriction of the cohort to pregnancy planners. WIDER IMPLICATIONS OF THE FINDINGS:Further evaluation of the potential deleterious effects of bicycling on male fertility, with additional consideration of the influence of bike seat type and BMI, may be warranted. STUDY FUNDING/COMPETING INTEREST(S):This study was funded by NICHD Grants R21-HD072326, R01-HD086742, R01 HD105863, and R03-HD094117. These funding bodies had no involvement in the: study design; collection, analysis, and interpretation of data; writing of the report; or decision to submit the article for publication. L.A.W. serves as a paid consultant for AbbVie, Inc. and the Bill and Melinda Gates Foundation. She also receives in-kind donations for primary data collection in Pregnancy Study Online (PRESTO) from Swiss Precision Diagnostics (home pregnancy tests) and Kindara.com (fertility apps). All of these relationships are for work unrelated to this manuscript. M.L.E. is an advisor for and holds stock in Legacy, Doveras, VSeat, Hannah, Illumicell, HisTurn, & Next. The other authors have no competing interests to declare. TRIAL REGISTRATION NUMBER:N/A.

More than one million sexually transmitted infections (STIs) are acquired every day worldwide. They are commonly caused by Chlamydia trachomatis (CT), herpes simplex virus (HSV), or human papillomavirus (HPV) and are suggested to contribute to female infertility. This scoping review aims to map and summarize existing literature on the association between a pre-pregnancy infection with CT, genital HSV, or HPV and female fertility.We searched two databases (PubMed, Embase) to identify published literature on the association between CT, genital HSV, or HPV infection and female fertility. We included full-text articles, published from 2002 to 2022, on pre-pregnancy infection with either CT, genital HSV, or HPV within a population of women of reproductive age. The study endpoint was either pregnancy, time-to-pregnancy, or infertility. The included studies were evaluated according to the Critical Appraisal Tool by Joanna Briggs Institute.Eight studies were eligible for the review. All of them investigated the association between a CT infection and fertility, while none of them investigated infections with genital HSV or HPV. Three studies found that a CT infection was associated with poorer female fertility, and one study found a similar association in a subgroup analysis of women with a pregnancy intention. Four studies indicated no association, although methodological differences between the studies preclude firm conclusions.This review revealed sparse literature investigating the association between CT, HPV, and HSV and subsequent female fertility. Prospective cohort studies with preconception assessments of these STIs are needed to determine the relation between STIs and subsequent fertility.

We estimated the effects of sleep duration, trouble sleeping, and job time (day, evening, shift, and night work) on fecundability, the per-cycle probability of conception. We analysed data from a preconception cohort study of 10 475 Danish females aged 18-45 years attempting to conceive. On baseline questionnaires, females reported on sleep duration (hours/day), trouble sleeping (never, sometimes, approx. 50% of the time, most of the time), and job time. Pregnancy status was ascertained from follow-up questionnaires completed every 8 weeks for up to 12 months. We used proportional probabilities regression models to estimate fecundability ratios (FRs), adjusted for potential confounders. Compared with 8 h/day of sleep, FRs were 0.94 for ≤6 h/day (95% CI, 0.83-1.08), 0.97 for 7 h/day (95% CI, 0.89-1.06), and 0.96 for ≥9 h/day (95% CI, 0.81-1.13). Compared with no trouble sleeping, FRs were 1.00 (95% CI, 0.94-1.06) for trouble sleeping sometimes, 0.94 (95% CI, 0.86-1.03) for trouble sleeping approx. 50% of the time, and 0.95 (95% CI, 0.82-1.10) for trouble sleeping most of the time. Relative to day work, FRs were 1.12 for shift work (95% CI, 1.04-1.20), 0.77 for night work (95% CI, 0.49-1.22) and 1.10 for evening work (95% CI, 0.91-1.33). Self-reported sleep duration and trouble sleeping were not appreciably associated with fecundability. Shift work was associated with a slightly higher fecundability, while night work was associated with slightly lower fecundability, although associations were imprecise. Potential limitations include misclassification of sleep and residual or unmeasured confounding.

STUDY QUESTION: Is cervical intraepithelial neoplasia (CIN) associated with reduced fecundability, defined as the probability of conceiving per menstrual cycle? SUMMARY ANSWER: Overall, we observed no meaningful association between CIN and fecundability, regardless of surgical status, although a recent diagnosis of moderate or severe CIN might be associated with slightly reduced fecundability for 2 years after diagnosis. WHAT IS KNOWN ALREADY: About 15% of couples experience infertility. Few studies have examined the influence of CIN on fertility, and the results have been inconsistent. No study has investigated the association between fecundability and pathologist-reported CIN diagnoses, particularly with respect to the recency of the specific CIN diagnoses. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included 9586 women trying to conceive. The women were enrolled from 1 June 2007 to 3 February 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women were invited to complete a baseline questionnaire and bimonthly follow-up questionnaires for up to 12 months or until pregnancy occurred. Data on cervical cytologies and biopsies were retrieved from The National Pathology Registry (DNPR), which holds records of all cervical specimens examined in Denmark. Women were categorized based on their most severe diagnosis of CIN: no lesion, other cervical changes, mild CIN (CIN1), or moderate/severe CIN (CIN2+) with or without surgery. To investigate the association between CIN and fecundability, we computed fecundability ratios (FR) and 95% confidence intervals (CI) using a proportional probabilities regression model. We adjusted for age at study entry, partner age, body mass index, smoking status, timing of intercourse, parity, education, number of sexual partners, and household income. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with no lesion, the adjusted FRs (95% CI) for the association between CIN and fecundability were: other cervical lesions, 0.97 (0.91-1.04); CIN1, 1.04 (0.96-1.13); CIN2+ no surgery, 1.00 (0.82-1.22); and CIN2+ with surgery 0.99 (0.89-1.10). The FRs (95% CI) for a recent diagnosis (<2 years) of CIN were 0.98 (0.86-1.11) for other cervical lesions; 1.13 (0.99-1.29) for CIN1; 0.89 (0.62-1.26) for CIN2+ no surgery and 0.91 (0.75-1.10) for CIN2+ with surgery compared with the no lesion group. LIMITATIONS, REASONS FOR CAUTION: In the analyses, we adjusted for several covariates related to the women. However, we had little information on the male partners which could lead to unmeasured confounding as fecundability is a couple-based measure of fertility. Furthermore, a CIN diagnosis may not be constant as it may regress or progress spontaneously; therefore, it is possible that we have misclassified some women, especially women categorized as having normal cells or CIN1. WIDER IMPLICATIONS OF THE FINDINGS: Our results contribute important knowledge to women who are concerned about their future fertility after receiving a CIN diagnosis.

BackgroundThe use of fertility indicators to predict ovulation has largely been studied for contraceptive purposes, while less so as fertility-promoting tools.ObjectiveTo investigate the association between fertility indicators and fecundability in Danish women trying to conceive.MethodsWeb-based preconception cohort study. We analysed data from 11,328 females aged 18-49 years trying to conceive without fertility treatment for <= 6 menstrual cycles, from the Danish SnartGravid.dk and SnartFor ae ldre.dk cohorts (2007-2023). Participants reported the use of fertility indicators (counting days since the last menstrual period, cervical fluid monitoring, urinary ovulation testing, feeling ovulation, using a smartphone fertility app and measuring basal body temperature [BBT]). Time to pregnancy was measured in menstrual cycles ascertained by self-reported pregnancy status. We estimated fecundability ratios (FR) and 95% confidence intervals (CIs) using proportional probabilities regression models adjusted for age, socio-economic position, health indicators, reproductive history and gynaecological factors.ResultsFertility indicators were used by 63.3% of participants at study entry. Counting days was the most common (46.9%), while measuring BBT was the least (3.0%). Other indicators ranged from 17.0% to 23.6%, with 69.7% using more than one indicator. Compared with non-use, use of any fertility indicator was associated with greater fecundability (adjusted FR 1.14, 95% CI 1.08, 1.19). Cervical fluid monitoring showed the strongest association (aFR 1.46, 95% CI 1.03, 2.07), followed by urinary ovulation testing (aFR 1.35, 95% CI 1.16, 1.58) and counting days (aFR 1.18, 95% CI 1.09, 1.29). Feeling ovulation and fertility apps were modestly associated with fecundability, while measuring BBT was not associated. Sensitivity analysis restricting to <= 2 cycles of attempt time and two cycles of follow-up showed an aFR for any indicator use of 1.21 (95% CI 1.13, 1.31).ConclusionIn this Danish preconception cohort, use of fertility indicators was associated with a higher fecundability, varying by type of indicator.

STUDY QUESTION:To what extent is socioeconomic status (SES), as measured by educational attainment and household income, associated with fecundability in a cohort of Danish couples trying to conceive?SUMMARY ANSWER:In this preconception cohort, lower educational attainment and lower household income were associated with lower fecundability after adjusting for potential confounders.WHAT IS KNOWN ALREADY:Approximately 15% of couples are affected by infertility. Socioeconomic disparities in health are well established. However, little is known about socioeconomic disparity and its relation to fertility.STUDY DESIGN, SIZE, DURATION:This is a cohort study of Danish females aged 18-49 years who were trying to conceive between 2007 and 2021. Information was collected via baseline and bi-monthly follow-up questionnaires for 12 months or until reported pregnancy.PARTICIPANTS/MATERIALS, SETTING, METHODS:Overall, 10 475 participants contributed 38 629 menstrual cycles and 6554 pregnancies during a maximum of 12 cycles of follow-up. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs.MAIN RESULTS AND THE ROLE OF CHANCE:Compared with upper tertiary education (highest level), fecundability was substantially lower for primary and secondary school (FR: 0.73, 95% CI: 0.62-0.85), upper secondary school (FR: 0.89, 95% CI: 0.79-1.00), vocational education (FR: 0.81, 95% CI: 0.75-0.89), and lower tertiary education (FR: 0.87, 95% CI: 0.80-0.95), but not for middle tertiary education (FR: 0.98, 95% CI: 0.93-1.03). Compared with a monthly household income of >65 000 DKK, fecundability was lower for household income <25 000 DKK (FR: 0.78, 95% CI: 0.72-0.85), 25 000-39 000 DKK (FR: 0.88, 95% CI: 0.82-0.94), and 40 000-65 000 DKK (FR: 0.94, 95% CI: 0.88-0.99). The results did not change appreciably after adjustment for potential confounders.LIMITATIONS, REASONS FOR CAUTION:We used educational attainment and household income as indicators of SES. However, SES is a complex concept, and these indicators may not reflect all aspects of SES. The study recruited couples planning to conceive, including the full spectrum of fertility from less fertile to highly fertile individuals. Our results may generalize to most couples who are trying to conceive.WIDER IMPLICATIONS OF THE FINDINGS:Our results are consistent with the literature indicating well-documented inequities in health across socioeconomic groups. The associations for income were surprisingly strong considering the Danish welfare state. These results indicate that the redistributive welfare system in Denmark does not suffice to eradicate inequities in reproductive health.STUDY FUNDING/COMPETING INTEREST(S):The study was supported by the Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, and the National Institute of Child Health and Human Development (RO1-HD086742, R21-HD050264, and R01-HD060680). The authors declare no conflict of interest.TRIAL REGISTRATION NUMBER:N/A.

Spontaneous abortion (SAB), defined as a pregnancy loss before 20 weeks of gestation, affects up to 30% of conceptions, yet few modifiable risk factors have been identified. We estimated the effect of ambient air pollution exposure on SAB incidence in Pregnancy Study Online (PRESTO), a preconception cohort study of North American couples who were trying to conceive. Participants completed questionnaires at baseline, every 8 weeks during preconception follow-up, and in early and late pregnancy. We analyzed data on 4643 United States (U.S.) participants and 851 Canadian participants who enrolled during 2013-2019 and conceived during 12 months of follow-up. We used country-specific national spatiotemporal models to estimate concentrations of particulate matter <2.5 μm (PM2.5), nitrogen dioxide (NO2), and ozone (O3) during the preconception and prenatal periods at each participant's residential address. On follow-up and pregnancy questionnaires, participants reported information on pregnancy status, including SAB incidence and timing. We fit Cox proportional hazards regression models with gestational weeks as the time scale to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of time-varying prenatal concentrations of PM2.5, NO2, and O3 with rate of SAB, adjusting for individual- and neighborhood-level factors. Nineteen percent of pregnancies ended in SAB. Greater PM2.5 concentrations were associated with a higher incidence of SAB in Canada, but not in the U.S. (HRs for a 5 μg/m3 increase = 1.29, 95% CI: 0.99, 1.68 and 0.94, 95% CI: 0.83, 1.08, respectively). NO2 and O3 concentrations were not appreciably associated with SAB incidence. Results did not vary substantially by gestational weeks or season at risk. In summary, we found little evidence for an effect of residential ambient PM2.5, NO2, and O3 concentrations on SAB incidence in the U.S., but a moderate positive association of PM2.5 with SAB incidence in Canada.

Abstract Background Little is known about potential health effects of eating organic food in relation to reproduction. Objective We examined associations between organic food consumption and fecundability. Methods Data were derived from a preconception cohort study of Danish couples trying to conceive (SnartForældre.dk, SF). Participants completed a baseline questionnaire on socio‐demographics, anthropometrics and lifestyle and a validated food‐frequency questionnaire, which included questions on proportions of organic food consumed within six food groups. Participants were followed up with bimonthly questionnaires for up to 12 months or until pregnancy. Analyses were restricted to 2061 participants attempting pregnancy for ≤6 cycles at enrollment and 1303 with <3 cycles. Fecundability ratios (FRs) and 95% confidence intervals (CI) were estimated by proportional probabilities regression models adjusted for potential confounders including age, lifestyle and socioeconomic factors. Associations were examined for vegetables, fruits, cereals, dairy products, eggs and meat, separately, and for the overall pattern of organic food consumption (organic sum score). Results The final analytic sample comprised 2069 participants. In the full cohort, organic food consumption was not meaningfully associated with fecundability. Among participants <3 cycles of pregnancy attempt at study entry (n = 1303), the FR was 1.11 (95% CI 0.93, 1.33) for the category ‘less than half’, for ‘more than half’ the FR was 1.17 (95% CI 0.99, 1.38) and for ‘almost everything’ the FR was 1.12 (95% CI 0.97, 1.28). Conclusion Higher consumption of organic foods was not meaningfully associated with fecundability, although slightly greater fecundability was seen among participants with <3 cycles of pregnancy attempt time.

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). 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 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 (R1 prescription vs. none: adjusted FR 1/4 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. (Fertil Steril (R) 2023;120:650-59. (c) 2023 by American Society for Reproductive Medicine.) El resumen esta disponible en Espanol al final del articulo.

Objective Adult overweight is associated with increased risk of diverticular disease (DD). We investigated associations between birthweight and childhood body mass index (BMI) and DD. Methods Cohort study of 346,586 persons born during 1930–1996 with records in the Copenhagen School Health Records Register. Data included birthweight, and height and weight from ages 7 through 13. We used Cox proportional hazard regression to examine associations between birthweight and BMI z -scores and DD registered in the Danish National Patient Registry. Due to non-proportionality, we followed participants from age 18–49 and from age 50. Results During follow-up, 5459 (3.2%) women and 4429 (2.5%) men had DD. For low and high BMI in childhood, we observed a higher risk of DD before age 50. Among women with z -scores <0 at age 13, the hazard ratio (HR) was 1.16 [95% confidence interval (CI): 0.98–1.39] per one-point lower z -score. For z -scores ≥0 at age 13, the HR was 1.30 (95% CI: 1.11–1.51) per one-point higher z -score. Among men with z -scores <0 at age 13, the HR was 1.02 (95% CI: 0.85–1.22). For z -scores ≥0 at age 13, the HR was 1.54 (95% CI: 1.34–1.78). Z -scores ≥0 were not associated with DD after age 50. Among women only, birthweight was inversely associated with DD before age 50 [HR = 0.90 (95% CI: 0.83–0.99) per 500 g higher birthweight]. Conclusion BMI z -scores below and above zero in childhood were associated with higher risk of DD before age 50. In addition, we observed lower risk of DD among women, the higher their birthweight.

Abstract Study question Does a previous infection with Chlamydia trachomatis (CT) or genital herpes simplex virus (HSV) affect fecundability, and does recency of infection play a role? Summary answer Previous infection with CT or HSV in women was not appreciably associated with fecundability. However, a recent CT infection was associated with slightly lower fecundability. What is known already Worldwide, 1 million people contract sexually transmitted infections (STIs) every day. CT and genital HSV infections are among the most common STIs. Untreated CT in women can cause pelvic inflammatory disease (PID), which can lead to scarring and narrowing of the fallopian tubes and the lower uterus, thus complicating the ability to conceive. Also, an association between genital HSV in women and PID has been suggested. However, it is uncertain to what extent CT and HSV infections in women are associated with fecundability, defined as the per-cycle probability of conception, and whether recency of the infection plays a role. Study design, size, duration We conducted a prospective cohort study of female participants included in two Danish preconception cohorts: SnartGravid.dk (‘Soon Pregnant’, 2007-2011) and SnartForældre.dk (‘Soon Parents’, 2011-ongoing). At enrollment, participants had to be non-pregnant, aged 18-45 years, in a relationship with a male partner, not using contraception or fertility treatment, and trying to conceive. Participants completed a baseline questionnaire and bimonthly follow-up questionnaires until conception or up to 12 months after study entry. Participants/materials, setting, methods We analyzed data from 10475 women. At study entry, participants reported if they had ever been diagnosed (including year of first diagnosis) with CT or HSV. Fecundability ratios (FRs) were calculated using proportional probability regression models and 95% confidence intervals (CIs). The analyses were adjusted for age, income, educational attainment, other STIs, and smoking, reported at study entry. The reference groups were either women with no CT or no HSV diagnosis. Main results and the role of chance At study entry, 2603 (24.9%) of participants reported a history of infection with CT, and 766 (7.3%) with HSV. Using life table methods, 84.7% of participants conceived within 12 cycles of follow-up. Compared with the reference group, the adjusted FR for women ever diagnosed with CT was 0.98 (CI: 0.93-1.04) and 0.96 (CI: 0.88-1.06) for women ever diagnosed with HSV. Compared with the reference group, a recent CT infection was associated with slightly lower fecundability: adjusted FRs for women diagnosed 0-2 years, 2-5 years, and more than 5 years before study entry were 0.84 (CI: 0.71-0.99), 1.01 (CI: 0.90-1.12), and 1.00 (CI: 0.93-1.07), respectively. The association between recency of a HSV infection compared to the reference group was less evident: adjusted FRs for 0-2 years, 2-5 years, and more than 5 years since study entry were 0.93 (CI: 0.72-1.21), 0.97 (CI: 0.77-1.22), and 0.91 (0.75-1.09), respectively. Limitations, reasons for caution Misclassification of exposure is possible, as CT and HSV infections are often asymptomatic and hence undiagnosed. In addition, self-report may have resulted in misclassification of infection type and year. Further, we lacked information on severity or frequency of infections. Wider implications of the findings Women diagnosed with STIs often experience psychological distress concerning their future ability to conceive. Our finding of no overall association between previous diagnoses of CT or HSV may reassure women wanting to conceive. Still, testing for STIs remains important because untreated infections can damage the female reproductive system. Trial registration number Not applicable

Abstract Study question Does the gestational weight gain trajectory differ across levels of time-to-pregnancy (TTP) for spontaneously conceived pregnancies and pregnancies conceived by assisted reproductive technology (ART)? Summary answer Women with ART pregnancies had lower weekly weight gain during the third trimester compared with women with spontaneous conceptions with TTP ≤3. What is known already Studies suggest that both prolonged TTP and conception by ART may increase the risk of pregnancy complications and affect perinatal outcomes such as birthweight. Suboptimal gestational weight gain might further increase the risk of adverse pregnancy outcomes. However, it remains unclear whether there may be differences in gestational weight gain according to TTP and ART, which contribute to the subsequent risk of adverse pregnancy outcomes. Study design, size, duration We studied 69,121 singleton planned pregnancies contributed by 60,847 women participating in the Norwegian Mother, Father and Child Cohort Study. Participants completed questionnaires at 15 weeks’ gestation (study entry), 30 weeks’ gestation, and six months postpartum on sociodemographic, reproductive, and behavioral factors. Participants reported their TTP, and up to four weight measurements and corresponding gestational age from preconception through delivery. We identified use of ART in the Medical Birth Registry of Norway. Participants/materials, setting, methods We fitted gestational weight gain trajectories using mixed-effects linear regression models and included an interaction term between time (gestational weeks) and the exposure groups, TTP ≤3 (reference); TTP 4-6; TTP 7-11, TTP ≥12 months, and ART, to assess differences across levels of TTP and conception by ART. The analyses were adjusted for maternal age at start of pregnancy, pre-pregnancy height, educational attainment, pre-pregnancy smoking, parity, and gestational age at birth. Main results and the role of chance The adjusted average weekly weight gain was -15g (95% CI: −19; −12) during the first trimester, 620g (95% CI: 615; 624) during the second trimester, and 491g (95% CI: 489; 494) during the third trimester. When we compared differences in average weekly weight change during the first trimester, we observed little difference between the exposure groups. During the second trimester, compared with TTP≤3 months women with TTP 4-6 months, TTP 7-11 months or TTP ≥12 months gained on average 7g (95% CI: −18; 3), 19g (95% CI: −33; −5) and 15g (95% CI: −29; −1) less per week, respectively, whereas women with ART pregnancies gained 11g more per week (95% CI: −13; 34). However, the results for TTP 4-6 and ART pregnancies were imprecise. During the third trimester, average weekly weight gain did not differ according to TTP for spontaneous conceptions, while women who conceived after ART gained 35g (95% CI: −49; −22) less than women with TTP≤3 each week. Limitations, reasons for caution Because TTP and gestational weight gain were self-reported, non-differential misclassification may have influenced our results. Wider implications of the findings Decelerated weight gain during the third trimester in ART pregnancies compared with women who conceived spontaneously within 3 months might be associated with adverse pregnancy outcomes. Although our findings are imprecise and need to be replicated, monitoring gestational weight gain trajectories might support identification of pregnancies at increased risk. Trial registration number Not applicable

Purpose:Humans are living longer and may develop multiple chronic diseases in later life. The Better Health in Late Life cohort study aims to improve our understanding of the risks and outcomes of multimorbidity in the Danish population.Methods:A randomly-selected sample of Danish residents who were 50-65 years of age received a questionnaire and an invitation to participate in this study. Respondents completed an online survey between October 2021 and January 2022 which addressed topics that included self-assessed health, mental health, sleep, specific medical conditions, use of painkillers, diet, alcohol consumption, smoking, physical activity, and body composition. This information was linked to the Danish health and social registries (some established in 1943 and onwards) that maintain data on filled prescriptions, hospital records, socioeconomic status, and health care utilization.Results:Responses were received from 115,431 of the 301,244 residents invited to participate (38%). We excluded respondents who answered none of the questions as well as those who provided no information on sex or indicated an age other than 50-65 years. Of the 114,283 eligible respondents, 54.8% were female, 30.3% were overweight, and 16.7% were obese. Most participants reported a weekly alcohol consumption of less than seven units and 13.3% were current smokers; 5.2% had a history of hospitalization for solid cancer, and 3.0%, 2.3%, 2.0%, and 0.9% reported chronic pulmonary disease, diabetes, stroke, and myocardial infarction, respectively. The most frequently filled prescriptions were for medications used to treat the nervous system and cardiovascular diseases (38.1% and 37.4%, respectively).

STUDY QUESTION:To what extent is dietary folate intake and total folate intake (dietary and supplemental intakes) associated with fecundability, the per cycle probability of conception?SUMMARY ANSWER:Preconception dietary folate intake was positively associated with fecundability in a monotonic pattern.WHAT IS KNOWN ALREADY:Supplemental folic acid has been associated with improved fertility, but little is known about the relation between dietary folate and fecundability.STUDY DESIGN, SIZE, DURATION:A prospective cohort study including 9559 women trying to conceive without fertility treatment and enrolled in the period 2013-2020.PARTICIPANTS/MATERIALS, SETTING, METHODS:We used data from two internet-based prospective cohort studies of pregnancy planners from Denmark, where folic acid fortification is not performed (SnartForældre.dk (SF); n = 3755) and North America, where the food supply is fortified with folic acid (Pregnancy Study Online (PRESTO); n = 5804). Women contributed menstrual cycles at risk until they reported conception or experienced a censoring event. We used proportional probabilities regression models to compute fecundability ratios (FRs) and 95% CI, adjusting for potential confounders.MAIN RESULTS AND THE ROLE OF CHANCE:Compared with a dietary folate intake ≥400 µg/day, the adjusted FRs for women in SF were 0.92 (95% CI: 0.85-0.99) for intake 250-399 µg/day, and 0.80 (95% CI: 0.68-0.94) for intake of <250 µg/day. The corresponding FRs in PRESTO were 0.95 (95% CI: 0.89-1.01) and 0.81 (95% CI: 0.65-1.00). Compared with the highest level of total folate intake (diet folate ≥400 µg/day plus folic acid supplementation), in both cohorts fecundability was lowest among women with the lowest dietary intake <250 µg/day dietary folate and no supplementation (FR: 0.76, 95% CI: 0.59-0.98 [SF] and 0.49, 95% CI: 0.31-0.77 [PRESTO]). Further, total intake dietary folate <250 µg/day plus supplementation was associated with reduced fecundability for SF participants (FR; 0.79, 95% CI: 0.65-0.98) and for PRESTO participants (FR; 0.92, 95% CI: 0.72-1.16).LIMITATIONS, REASONS FOR CAUTION:It is unknown whether dietary folate and folic acid intake affect fecundability on its own or if there is an interaction with other micronutrients provided in healthy diet. Thus, the observed associations may not reflect dietary folate intake alone, but overall healthy diet.WIDER IMPLICATIONS OF THE FINDINGS:Recommendations for preconception dietary folate intake and folic acid supplementation are of importance not only to prevent neural tube defects but also to enhance fecundability.STUDY FUNDING/COMPETING INTEREST(S):The study was supported by the National Institute of Child Health and Human Development (R01-HD086742). The authors report no competing interests.TRIAL REGISTRATION NUMBER:N/A.

Background Spontaneous abortion (SAB)-pregnancy loss before the 20th week of gestation-has adverse psychological and physical sequelae. Some medical conditions known to affect insulin sensitivity, including polycystic ovary syndrome and diabetes, can affect the risk of SAB. No prior studies have examined glycemic load and incidence of SAB in populations without conditions known to affect insulin sensitivity. Objectives We prospectively evaluated the association between preconception glycemic load and intake of carbohydrates, dietary fiber, and added sugar and risk of SAB. Methods During 2013-2020, we recruited pregnancy planners from Denmark (SnartForaeldre.dk; SF) and the United States and Canada (Pregnancy Study Online; PRESTO). Participants completed a baseline questionnaire and a cohort-specific FFQ evaluated for validity. We estimated preconception glycemic load and intake of carbohydrates, dietary fiber, and added sugar from individual foods and mixed recipes. We included 2238 SF and 4246 PRESTO participants who reported a pregnancy during the course of the study. SAB data were derived from questionnaires and population registries. We used Cox proportional hazards regression to estimate HRs and 95% CIs. Results In the study population, 15% of SF participants and 22% of PRESTO participants experienced SAB. Across both cohorts, there was no appreciable association between glycemic load, carbohydrate quality, dietary fiber, or added sugar intake and SAB. Compared with daily mean glycemic load <110, the HR for women with daily mean glycemic load >= 130 was 0.76 (95% CI: 0.52, 1.10) in SF and 1.01 (95% CI: 0.86, 1.19) in PRESTO. Conclusions Diets with high glycemic load, carbohydrates, and added sugars were not consistently associated with risk of SAB in parallel analyses of 2 preconception cohort studies of women in North America and Denmark.

Evidence on the influence of modifiable risk factors on spontaneous abortion (SAB) is scarce. We investigated associations for adherence to national dietary guidelines and a healthy Nordic diet with first-trimester (≤ 12 weeks’ gestation) SAB in a Danish cohort of couples trying to conceive. Participants completed a questionnaire on sociodemographics, lifestyle and reproductive history and a validated food frequency questionnaire (FFQ). We ascertained pregnancies from follow-up questionnaires and restricted analyses to 3,043 women who became pregnant. We assessed adherence to the Danish Dietary Guidelines Index (DDGI, range of 0–6, from low to high), covering intake of fruit, vegetables, fish, red and processed meat, whole grains, saturated fat and added sugar. The Healthy Nordic Food Index (HNFI, range 0–6) covered intake of fish, cabbage, rye bread, apples, pears, root vegetables and oatmeal. Pregnancy outcomes were identified through Danish medical registries or self-reported. We used Cox proportional hazards regression to compute hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for sociodemographics and lifestyle. Fifteen percent of participants had a first-trimester SAB. Compared with a DDGI score < 3, adjusted HRs (95% CIs) for scores 3 to < 4, 4 to  < 5 and ≥ 5 were 0.85 (0.59–1.23), 0.78 (0.54–1.12) and 0.71 (0.44–1.13), respectively. Compared with an HNFI score < 2, adjusted HRs (95% CIs) for scores 2 to < 3, 3 to < 4, 4 to < 5 and ≥ 5 were 0.84 (0.62–1.15), 0.88 (0.66–1.19), 0.94 (0.69–1.28) and 0.69 (0.49–0.96), respectively. Greater pre-pregnancy adherence to Danish dietary guidelines or a healthy Nordic diet was associated with a lower rate of first-trimester SAB, although estimates were imprecise.

Diet quality is increasingly recognized as important for human reproductive capacity. We studied the association between intake of protein-rich foods and risk of spontaneous abortion (SAB). During 2013–2020, we recruited pregnancy planners from the United States and Canada (Pregnancy Study Online; PRESTO) and Denmark (SnartForaeldre.dk; SF). Participants completed a baseline questionnaire and a validated cohort-specific food frequency questionnaire. We estimated preconception intake of red meat, poultry, processed meat, seafood, eggs, plant-based proteins, and dairy from individual foods and mixed recipes. We included 4,246 PRESTO and 2,953 SF participants who reported a pregnancy during the study. Data on SAB were derived from questionnaires and population registries. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CI), representing the effect of substituting one type of protein-rich food for another. SAB risk was 23% in PRESTO and 16% in SF. In PRESTO, substitution of seafood with other protein-rich foods was associated with higher SAB risk [for example, the HR for replacing 100 g of seafood/week with 100 g of red meat was 1.10 (95% CI 1.00, 1.20)]. In contrast, in SF, substituting seafood with other protein-rich foods was associated with lower SAB risk [HR for replacing 100 g of seafood/week with 100 g of red meat was 0.89 (95% CI 0.82, 0.98)]. Other protein-rich food substitutions were not meaningfully associated with SAB risk. Preconception intake of protein-rich foods was largely unrelated to SAB risk, with the exception of seafood, which was associated with higher risk of SAB in Denmark, but a lower risk in North America.