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The article discusses the results of a study on the effects of per- and polyfluoroalkyl substances (PFAS) on the reproductive health of women. Topics mentioned include the relation of PFAS and anti-mullerian hormone (AMH) as a biomarker of ovarian reserve among noncontraceptive women, the use of AMH in predicting the timing of menopause and menstrual cycle, and the routes of exposure to PFAS.

Purpose: The aim of this study was to evaluate the association between menstrual cycle characteristics in early life and adulthood and fecundability.Methods: Pregnancy Study Online (PRESTO) is an Internet-based preconception cohort study of pregnancy planners from the United States and Canada. During the preconception period, we enrolled 2189 female pregnancy planners aged 21-45 years who had been attempting conception for ≤6 cycles. Women self-reported menstrual cycle characteristics via an online baseline questionnaire, and pregnancy status was ascertained through bimonthly follow-up questionnaires. Proportional probabilities models were used to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), adjusting for potential confounders.Results: Compared with usual menstrual cycle lengths of 27-29 days, cycle lengths of <25 (FR = 0.81, 95% CI: 0.54-1.22) and 25-26 days (FR = 0.92, 95% CI: 0.75-1.14) were associated with reduced fecundability. Compared with women who reached menarche at the age of 12-13 years, those who reached menarche at <12 years had reduced fecundability (FR = 0.87, 95% CI: 0.76-0.99). Women whose cycles never regularized after menarche (FR = 0.93, 95% CI: 0.81-1.06) had slightly reduced fecundability compared with women whose cycles regularized within 2 years of menarche. Bleed length and heaviness of bleeding were not appreciably associated with fecundability.Conclusions: Menstrual cycle characteristics, specifically cycle length and age at menarche, may act as markers of fertility potential among pregnancy planners. [ABSTRACT FROM AUTHOR]

Chemical hair straighteners ("relaxers") are used by millions of North Americans, particularly women of color. Hair relaxers may contain endocrine-disrupting compounds, which can harm fertility. We evaluated the association between hair relaxer use and fecundability among 11,274 participants from Pregnancy Study Online (PRESTO), a North American preconception cohort study. During 2014–2022, participants completed a baseline questionnaire in which they reported their history of relaxer use and completed follow-up questionnaires every 8 weeks for 12 months or until pregnancy, whichever came first. We used multivariable-adjusted proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs). Relative to never use, fecundability was lower among current (FR = 0.81, 95% CI: 0.64, 1.03) and former (FR = 0.89, 95% CI: 0.81, 0.98) users of hair relaxers. FRs for first use of hair relaxers at ages <10, 10–19, and ≥20 years were 0.73 (95% CI: 0.55, 0.96), 0.93 (95% CI: 0.83, 1.04), and 0.85 (95% CI: 0.74, 0.98), respectively. Fecundability was lowest among those with longer durations of use (≥10 years vs. never: FR = 0.71, 95% CI: 0.54, 0.91) and more frequent use (≥5 times/year vs. never: FR = 0.82, 95% CI: 0.60, 1.11), but associations were nonmonotonic. In this preconception cohort study, use of chemical hair straighteners was associated with slightly reduced fecundability. [ABSTRACT FROM AUTHOR]

To assess the effect of randomization to FertilityFriend.com , a mobile computing fertility-tracking app, on fecundability. Parallel non-blinded randomized controlled trial nested within the Pregnancy Study Online (PRESTO), a North American preconception cohort. Female participants aged 21 to 45 years attempting conception for ≤6 menstrual cycles at enrolment (2013–2019). Randomization (1:1) of 5532 participants to receive a premium Fertility Friend (FF) subscription. Fecundability (per-cycle probability of conception). Participants completed bimonthly follow-up questionnaires until pregnancy or a censoring event, whichever came first. We first performed an intent-to-treat analysis of the effect of FF randomization on fecundability. In secondary analyses, we used a per-protocol approach that accounted for adherence in each trial arm. In both analyses, we used proportional probabilities regression models to estimate fecundability ratios (FR) and 95% confidence intervals (CI) comparing those randomized vs. not randomized and applied inverse probability weights to account for loss-to-follow-up (intent-to-treat and per-protocol analyses) and adherence (per-protocol analyses only). Using life-table methods, 64% of the 2775 participants randomized to FF and 63% of the 2767 participants not randomized to FF conceived during 12 cycles; these respective percentages were each 70% among those with 0–1 cycles of attempt time at enrolment. Of those randomized to FF, 72% were defined as adherent (68% of observed menstrual cycles). In intent-to-treat analyses, there was no appreciable association overall (FR = 0.97; 95% CI, 0.90–1.04) or within strata of pregnancy attempt time at enrolment, age, education, or other characteristics. In per-protocol analyses, we observed little association overall (FR = 1.06; 95% CI, 0.99–1.14), but weak-to-moderate positive associations among participants who had longer attempt times at enrolment (FR = 1.15; 95% CI, 0.98–1.35 for 3–4 cycles; FR = 1.14; 95% CI, 0.87–1.48 for 5–6 cycles), were aged <25 years (FR = 1.29; 95% CI, 1.01–1.66), had ≤12 years of education (FR = 1.32; 95% CI, 0.92–1.89), or were non-users of hormonal contraception within 3 months before enrolment (FR = 1.10; 95% CI, 1.02–1.19). No appreciable associations were observed in intent-to-treat analyses. In secondary per-protocol analyses that accounted for adherence, randomization to FF was associated with slightly greater fecundability among selected subgroups of participants; however, these results are susceptible to unmeasured confounding. [ABSTRACT FROM AUTHOR]

Background: The human papillomavirus (HPV) vaccine was developed to prevent infection with strains of HPV that cause cervical cancer. While HPV infection has been associated with reduced semen quality and lower pregnancy rates in some studies, no studies have examined the relationship between HPV vaccination and fecundability. We hypothesize that HPV prevention via vaccination will protect fecundity.Methods: We analysed data from Pregnancy Study Online (PRESTO), a preconception cohort of North American pregnancy planners. Between 2013 and 2017, we followed 3483 female pregnancy planners and 1022 of their male partners for 12 months or until reported pregnancy, whichever came first. At baseline, participants reported whether they had been vaccinated against HPV and their age at vaccination. We estimated fecundability ratios (FR) and 95% confidence intervals (CI) using proportional probabilities models adjusted for sociodemographics, smoking, and abnormal Pap test before HPV vaccination (females only).Results: HPV vaccination was more prevalent among females (33.9%) than males (5.2%). There was little overall association between female vaccination (FR 0.98, 95% CI 0.90, 1.08) or male vaccination (FR 1.07, 95% CI 0.79, 1.46) and fecundability. Among females with a history of sexually transmitted infections or pelvic inflammatory disease (i.e. a group at high risk of exposure to HPV infection), those vaccinated against HPV had higher fecundability than those not vaccinated (FR 1.35, 95% CI 0.99, 1.86).Conclusion: Although HPV vaccination had little effect on fecundability overall, HPV vaccination was positively associated with fecundability among women with a history of sexually transmitted infections. [ABSTRACT FROM AUTHOR]

Study Question: To what extent is preconception use of pain-relieving medication associated with female fecundability?Summary Answer: Women who used naproxen or opioids had slightly lower fecundability than women who did not use any pain-relieving medications; use of acetaminophen, aspirin and ibuprofen was not appreciably associated with fecundability.What Is Known Already: Over-the-counter pain-relieving medications are commonly used by women of reproductive age in the USA. Studies investigating the effects of pain-relieving medication use on ovulation, implantation and fecundability have shown conflicting results.Study Design, Size, Duration: We analyzed data from an internet-based prospective cohort study of 2573 female pregnancy planners aged 21-45 years from the USA and Canada. Participants were enrolled and followed from June 2013 through September 2015. Participants completed a baseline questionnaire and bimonthly follow-up questionnaires until a reported pregnancy or for 12 months, whichever occurred first. Over 80% of participants completed at least one follow-up questionnaire.Participants/materials, Setting, Methods: Use of pain-relieving medication during the past month was assessed at baseline and on each follow-up questionnaire. Medications were categorized according to type (acetaminophen, aspirin, ibuprofen, naproxen and opioids) and total monthly dose. Self-reported pregnancy was assessed at each follow-up. Multivariable-adjusted fecundability ratios (FRs) and 95% CI were calculated using proportional probabilities regression. Models were adjusted for demographic, lifestyle and anthropometric factors; reproductive history; gynecologic morbidity; and indications for use of pain medications. Models were also run with and without adjustment for parity. After restricting to women with 6 or fewer months of attempt time at study entry, 1763 were included in the analyses.Main Results and the Role Of Chance: At baseline, 1279 (73%) women reported using ≥1 pain-relieving medications in the previous month. When compared with non-use of pain-relieving medications, FRs for use of naproxen and opioids at baseline were 0.78 (95% CI: 0.64-0.97) and 0.81 (95% CI: 0.60-1.10), respectively. A dose-response relation was observed between naproxen use and fecundability; FRs for use of <1500 and ≥1500 mg of naproxen were 0.85 (95% CI: 0.68-1.07) and 0.58 (95% CI: 0.36-0.94), respectively. Small numbers (n = 74) precluded the examination of opioid use by dose. Overall, there was little evidence of an association between fecundability and acetaminophen (FR 1.04, 95% CI: 0.92-1.18), aspirin (FR 1.00, 95% CI: 0.80-1.25), or ibuprofen (FR 1.00, 95% CI: 0.89-1.11). Similar results were observed when exposure information was updated over time.Limitations, Reasons For Caution: Numbers of opioid users were small. Information collected on reason for use of pain medications was not specific to each type of pain medication. Therefore, we cannot rule out confounding by indication as an explanation of these results.Wider Implications Of the Findings: Use of naproxen and opioids was associated with a small reduction in fecundability, but there was little association between other pain-relieving medications and fecundability.Study Funding/competing Interests: This study was supported through funds provided by National Institute of Child Health and Human Development, National Institute of Health (R21 HD072326, T32 HD052458). The authors have no conflicts of interest to disclose.Trial Registration Number: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Psychological stress is prevalent among reproductive‐aged men. Assessment of semen quality for epidemiological studies is challenging as data collection is expensive and cumbersome, and studies evaluating the effect of perceived stress on semen quality are inconsistent. Objective: To examine the association between perceived stress and semen quality. Material and methods: We analyzed baseline data on 644 men (1,159 semen samples) from two prospective preconception cohort studies during 2015–2021: 592 in Pregnancy Study Online (PRESTO) and 52 in SnartForaeldre.dk (SF). At study entry, men aged ≥21 years (PRESTO) and ≥18 years (SF) trying to conceive without fertility treatment completed a questionnaire on reproductive and medical history, socio‐demographics, lifestyle, and the 10‐item version of the Perceived Stress Scale (PSS; interquartile range [IQR] of scores: 0–40). After enrollment (median weeks: 2.1, IQR: 1.3–3.7), men were invited to perform in‐home semen testing, twice with 7–10 days between tests, using the Trak Male Fertility Testing System. Semen quality was characterized by semen volume, sperm concentration, and total sperm count. We fit generalized estimating equation linear regression models to estimate the percent difference in mean log‐transformed semen parameters by four PSS groups (<10, 10–14, 15–19, ≥20), adjusting for potential confounders. Results: The median PSS score and IQR was 15 (10–19), and 136 men (21.1%) had a PSS score ≥20. Comparing men with PSS scores ≥20 with <10, the adjusted percent difference was −2.7 (95% CI: −9.8; 5.0) for semen volume, 6.8 (95% CI: ‐10.9; 28.1) for sperm concentration, and 4.3 (95% CI: −13.8; 26.2) for total sperm count. Conclusion: Our findings indicate that perceived stress is not materially associated with semen volume, sperm concentration, or total sperm count. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Several studies indicate adverse effects of selected heat exposures on semen quality, but few studies have directly evaluated fertility as an endpoint. Objective: We evaluated prospectively the association between male heat exposures and fecundability, the per‐cycle probability of conception. Materials and methods: We analyzed data from 3041 couples residing in the United States or Canada who enrolled in a prospective preconception cohort study (2013–2021). At enrollment, males reported on several heat‐related exposures, such as use of saunas, hot baths, seat heaters, and tight‐fitting underwear. Pregnancy status was updated on female follow‐up questionnaires every 8 weeks until conception or a censoring event (initiation of fertility treatment, cessation of pregnancy attempts, withdrawal, loss to follow‐up, or 12 cycles), whichever came first. We used proportional probabilities regression models to estimate fecundability ratios (FR) and 95% confidence intervals (CIs) for the association between heat exposures and fecundability, mutually adjusting for heat exposures and other potential confounders. Results: We observed small inverse associations for hot bath/tub use (≥3 vs. 0 times/month: FR = 0.87, 95% CI: 0.70–1.07) and fever in the 3 months before baseline (FR = 0.94, 95% CI: 0.79–1.12; one cycle of follow‐up: FR = 0.84, 95% CI: 0.64–1.11). Little association was found for sauna use, hours of laptop use on one's lap, seat heater use, time spent sitting, and use of tight‐fitting underwear. Based on a cumulative heat metric, FRs for 1, 2, 3, and ≥4 versus 0 heat exposures were 0.99 (95% CI: 0.87–1.12), 1.03 (95% CI: 0.89–1.19), 0.94 (95% CI: 0.74–1.19), and 0.77 (95% CI: 0.50–1.17), respectively. Associations were stronger among men aged ≥30 years (≥4 vs. 0 heat exposures: FR = 0.60, 95% CI: 0.34–1.04). Conclusion: Male use of hot tubs/baths and fever showed weak inverse associations with fecundability. Cumulative exposure to multiple heat sources was associated with a moderate reduction in fecundability, particularly among males aged ≥30 years. [ABSTRACT FROM AUTHOR]

Purpose: To prospectively examine the association between time-to-pregnancy (TTP) and postpartum depression (PPD) and determine whether perceived stress during early pregnancy mediated this association.Methods: In Pregnancy Study Online, an internet-based preconception cohort study of pregnancy planners, participants completed questionnaires every 8 weeks for up to 12 months or conception, during pregnancy, and at postpartum. A total of 2643 women provided information on sociodemographic factors, reproductive history, and stress (i.e., Perceived Stress Scale [PSS]) during preconception and early pregnancy (completed at ∼4-12 weeks' gestation) and on postpartum depressive symptoms (i.e., Edinburgh Postnatal Depression Scale [EPDS]) at ∼6 months postpartum. We used multivariable modified Poisson regression models to estimate risk ratios and 95% confidence intervals (CIs) for the association between TTP (<3, 3-5, 6-11, ≥12 menstrual cycles) and PPD (EPDS score ≥13). Causal mediation analyses assessed the mediating role of early pregnancy PSS scores.Results: 10.6% of women had EPDS scores indicating possible PPD (≥13). Compared with women who took less than 3 cycles to conceive, risk ratios for those who took 3-5, 6-11, and greater than or equal to 12 were 1.06 (95% CI: 0.77, 1.45), 1.24 (95% CI: 0.90, 1.70), and 1.31 (95% CI: 0.87, 1.99), respectively. Approximately 30% of the association between infertility (TTP ≥ 12) and PPD was mediated by early pregnancy PSS.Conclusions: There was a modest positive dose-response association between delayed conception and PPD. Perceived stress in early pregnancy explained a small proportion of this association. However, given the width of the CIs, chance cannot be ruled out as an explanation for the observed association. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Some studies indicate that Black women have higher exposure to multiple non-persistent endocrine disrupting chemicals (EDCs) than white women, but little is known about correlates of exposure to EDC mixtures. Using baseline data from a prospective cohort study of reproductive-aged Black women (N = 751), we characterized profiles of EDC mixtures and identified correlates of exposure. At baseline, we quantified biomarkers of 16 phthalates, 7 phenols, 4 parabens, and triclocarban in urine and collected covariate data through self-administered questionnaires and interviews. We used principal component (PC) analysis and k- means clustering to describe EDC mixture profiles. Associations between correlates and PCs were estimated as the mean difference (β) in PC scores, while associations between correlates and cluster membership were estimated as the odds ratio (OR) of cluster membership. Personal care product use was consistently associated with profiles of higher biomarker concentrations of non-persistent EDCs. Use of nail polish, menstrual and vaginal products (e.g., vaginal powder, vaginal deodorant), and sunscreen was associated with a mixture of phthalate and some phenol biomarkers using both methods. Current vaginal ring use, a form of hormonal contraception placed inside the vagina, was strongly associated with higher concentrations of high molecular weight phthalate biomarkers (k- means clustering: OR = 2.42, 95% CI = 1.28, 4.59; PCA: β = −0.32, 95% CI = −0.71, 0.07). Several dietary, reproductive, and demographic correlates were also associated with mixtures of EDC biomarkers. These findings suggest that personal care product use, diet, and contraceptive use may be sources of exposure to multiple non-persistent EDCs among reproductive-aged Black women. Targeted interventions to reduce exposure to multiple EDCs among Black women are warranted. [Display omitted] • Black women are exposed to a mixture of endocrine disrupting chemicals (EDCs) from consumer products. • Nail polish, sunscreen, and vaginal product use was associated with a mixture of phthalates, phenols, and parabens. • Targeted strategies to reduce use of certain products may help to reduce exposure to multiple EDCs among Black women. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Study Question: Can we derive adequate models to predict the probability of conception among couples actively trying to conceive?Summary Answer: Leveraging data collected from female participants in a North American preconception cohort study, we developed models to predict pregnancy with performance of ∼70% in the area under the receiver operating characteristic curve (AUC).What Is Known Already: Earlier work has focused primarily on identifying individual risk factors for infertility. Several predictive models have been developed in subfertile populations, with relatively low discrimination (AUC: 59-64%).Study Design, Size, Duration: Study participants were female, aged 21-45 years, residents of the USA or Canada, not using fertility treatment, and actively trying to conceive at enrollment (2013-2019). Participants completed a baseline questionnaire at enrollment and follow-up questionnaires every 2 months for up to 12 months or until conception. We used data from 4133 participants with no more than one menstrual cycle of pregnancy attempt at study entry.Participants/materials, Setting, Methods: On the baseline questionnaire, participants reported data on sociodemographic factors, lifestyle and behavioral factors, diet quality, medical history and selected male partner characteristics. A total of 163 predictors were considered in this study. We implemented regularized logistic regression, support vector machines, neural networks and gradient boosted decision trees to derive models predicting the probability of pregnancy: (i) within fewer than 12 menstrual cycles of pregnancy attempt time (Model I), and (ii) within 6 menstrual cycles of pregnancy attempt time (Model II). Cox models were used to predict the probability of pregnancy within each menstrual cycle for up to 12 cycles of follow-up (Model III). We assessed model performance using the AUC and the weighted-F1 score for Models I and II, and the concordance index for Model III.Main Results and the Role Of Chance: Model I and II AUCs were 70% and 66%, respectively, in parsimonious models, and the concordance index for Model III was 63%. The predictors that were positively associated with pregnancy in all models were: having previously breastfed an infant and using multivitamins or folic acid supplements. The predictors that were inversely associated with pregnancy in all models were: female age, female BMI and history of infertility. Among nulligravid women with no history of infertility, the most important predictors were: female age, female BMI, male BMI, use of a fertility app, attempt time at study entry and perceived stress.Limitations, Reasons For Caution: Reliance on self-reported predictor data could have introduced misclassification, which would likely be non-differential with respect to the pregnancy outcome given the prospective design. In addition, we cannot be certain that all relevant predictor variables were considered. Finally, though we validated the models using split-sample replication techniques, we did not conduct an external validation study.Wider Implications Of the Findings: Given a wide range of predictor data, machine learning algorithms can be leveraged to analyze epidemiologic data and predict the probability of conception with discrimination that exceeds earlier work.Study Funding/competing Interest(s): The research was partially supported by the U.S. National Science Foundation (under grants DMS-1664644, CNS-1645681 and IIS-1914792) and the National Institutes for Health (under grants R01 GM135930 and UL54 TR004130). In the last 3 years, L.A.W. has received in-kind donations for primary data collection in PRESTO from FertilityFriend.com, Kindara.com, Sandstone Diagnostics and Swiss Precision Diagnostics. L.A.W. also serves as a fibroid consultant to AbbVie, Inc. The other authors declare no competing interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Previous research indicates an association between higher-chlorinated polychlorinated biphenyls (PCBs) and type 2 diabetes (T2D). However, less is known about the extent to which PCB exposure in indoor air, composed primarily of lower-chlorinated PCBs, affects T2D risk. We assessed the association between indoor air exposure to PCBs in residential buildings and T2D incidence. The register-based 'Health Effects of PCBs in Indoor Air' (HESPAIR) cohort comprises 51,921 Danish residents of two residential areas with apartments built with and without PCB-containing materials (reference apartments). We assessed exposure status by combining register-based information on relocation history with extrapolated values of exposure based on PCB-measurements in indoor air from subsets of the apartments. T2D cases were identified in the Danish registers during 1977–2018. We estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression analyses with time-varying exposure. We identified 2737 incident T2D cases during the follow-up. Exposure to ≥3300 ng/m3 PCB × year (3rd tertile of PCB year) was associated with higher risk of T2D (HR 1.15, 95% CI 1.02–1.30) compared with exposure to <300 ng/m3 PCB × year (reference). However, among individuals with lower cumulated PCB year , the risk was similar to residents with exposure <300 ng/m3 PCB × year (300–899 ng/m3 PCB × year: HR 0.98, 95% CI 0.87–1.11; 900–3299 ng/m3 PCB × year: HR 0.96, 95% CI 0.83–1.10). We observed a marginally higher risk of T2D, but there was no evidence of an exposure-response relationship. The results should be interpreted with caution until confirmed in other independent studies of PCB exposure in indoor air. • Residents may be exposed to PCBs in indoor air in their private homes • Airborne PCB exposure has previously been associated with type 2 diabetes • PCB exposure in indoor air is associated with slightly higher type 2 diabetes risk [ABSTRACT FROM AUTHOR]

Background: Semen quality assessment in population-based epidemiologic studies presents logistical and financial challenges due to reliance on centralised laboratory semen analysis. The Trak Male Fertility Testing System is an FDA-cleared and validated at-home test for sperm concentration and semen volume, with a research use only sperm motility test. Here we evaluate the Trak System's overall utility among men participating in Pregnancy Study Online (PRESTO), a web-based study of North American couples planning pregnancy.Methods: US male participants aged ≥21 years with ≤6 months of pregnancy attempt time at study enrolment were invited to participate in the semen testing substudy after completing their baseline questionnaire. Consenting participants received a Trak Engine (battery-powered centrifuge) and two test kits. Participants shared their test results via smartphone images uploaded to online questionnaires. Data were then linked with covariate data from the baseline questionnaire.Results: Of the 688 men invited to participate, 373 (54%) provided consent and 271 (73%) completed at least one semen test result. The distributions of semen volume, sperm concentration, motile sperm concentration, total sperm count, and total motile sperm count were similar to 2010 World Health Organization (WHO) semen parameter data of men in the general population. The overall usability score for the Trak System was 1.4 on a 5-point Likert scale (1 = Very Easy, 5 = Difficult), and 92% of participants believed they performed the test correctly and received an accurate result. Lastly, men with higher motile sperm count were more likely to report feeling "at ease" or "excited" following testing, while men with low motile sperm count were more likely to report feeling "concerned" or "frustrated." Overall, 91% of men reported they would like to test again.Conclusions: The Trak System provides a simple and potentially cost-effective means of measuring important semen parameters and may be useful in population-based epidemiologic fertility studies. [ABSTRACT FROM AUTHOR]

We conducted a parallel, nonblinded randomized trial to assess whether offering home pregnancy tests (HPTs) to preconception cohort study participants influenced cohort retention or pregnancy detection. Pregnancy Study Online participants were female, aged 21–45 years, attempting pregnancy, and not using fertility treatment. At enrollment (2017–2018), 1,493 participants with 6 or fewer cycles of attempt time were randomly assigned with 50% probability to receive 12 Clearblue visual HPTs plus the standard protocol (n  = 720) or the standard protocol alone (n  = 773). Women completed bimonthly questionnaires for 12 months or until conception, whichever came first. In intent-to-treat analyses, retention (≥1 follow-up) was higher in the HPT arm (n  = 598; 83%) than the standard protocol arm (n  = 535 (69%); mean difference = 15%, 95% CI: 10, 19). Mean time at first pregnancy testing was identical in both arms (2 days before expected menses), as was mean gestational weeks at first positive pregnancy test (4 weeks). Conception was reported by 78% of women in the HPT arm and 75% in the standard protocol arm. Spontaneous abortion was reported by 21% in the HPT arm (mean gestational weeks = 7) and 21% in the standard protocol arm (mean gestational weeks = 6). Randomization of HPTs was associated with greater cohort retention but had little impact on incidence or timing of pregnancy detection. [ABSTRACT FROM AUTHOR]

• Pregnancy planners are a priority group for influenza vaccination. • The extent to which influenza vaccination affects fecundability is unclear. • Influenza vaccination was common (47% of females and 37% of males). • Our data indicate no adverse effect of influenza vaccination on fecundability. Although pregnancy planners are a priority group for influenza vaccination in the United States, little is known about the extent to which influenza vaccination affects fecundability. We analyzed data from Pregnancy Study Online (PRESTO), an ongoing preconception cohort study of North American pregnancy planners. During June 2013 to August 2019, 8654 female participants and 2137 of their male partners completed a baseline questionnaire and were followed until reported pregnancy, fertility treatment initiation, loss to follow-up, or 12 menstrual cycles of attempt time, whichever came first. At baseline, male and female participants reported whether they received an influenza vaccination in the past year and the date of vaccination. We used proportional probabilities regression models to estimate fecundability ratios (FR) and 95% confidence intervals (CI) comparing those who did and did not report influenza vaccination, adjusting for demographics, anthropometrics, behavioral factors, and medical history. Influenza vaccination in the past year was more common among female participants than male participants (47% vs. 37%). FRs were 1.04 (95% CI: 0.98–1.10) for female vaccination and 1.03 (95% CI: 0.93–1.14) for male vaccination. Among the 2137 couples with complete data on both partners, for 40% neither partner was vaccinated, 23% had female-only vaccination, 9% had male-only vaccination, and in 28% both partners were vaccinated. Compared with couples in which neither participant was vaccinated, FRs were 1.13 for female-only vaccination (95% CI: 0.99–1.29), 0.94 for male-only vaccination (95% CI: 0.78–1.12), and 1.07 when both partners were vaccinated (95% CI: 0.94–1.21). When restricted to recent vaccination before peak influenza season, results were similar. Our data indicate no adverse effect of influenza vaccination on fecundability. [ABSTRACT FROM AUTHOR]

Objective: Hirsutism, the presence of excess terminal hair in a male pattern, is a clinical marker of androgen excess in women. We used cross-sectional data from a North American preconception cohort study to evaluate the association between menstrual cycle characteristics and hirsutism.Study Design: Women aged 21-45 years were recruited to a North American cohort of pregnancy planners. On the baseline questionnaire, participants self-reported menstrual characteristics, which included menstrual regularity, cycle length, bleed length, and bleed heaviness. Participants provided a self-rating of hirsutism in nine distinct body areas using pictograms representing the modified Ferriman-Gallwey (mFG) score. Using their ratings, we calculated total mFG scores and defined hirsutism as mFG scores ≥8. We used log-binomial regression models to estimate prevalence ratios (PRs) for the association between menstrual characteristics and hirsutism assessed at baseline.Results: We included 5,542 women in the analytic cohort. Mean mFG score was 4.7, with 21.7 % reporting mFG scores ≥8. Compared with women with regular menstrual cycles, irregular cycles were positively associated with mFG ≥8 (PR 1.73, 95 % CI 1.56-1.91). Bleed lengths of ≥7 days compared with <3 days also showed a positive association with mFG score ≥8 (PR 1.59, 95 % CI 1.16-2.19), as did heavy bleeds (PR 1.42, 95 % CI 1.21-1.67) compared with moderate bleeds. Findings remained consistent when restricted to women without a prior diagnosis of polycystic ovary syndrome.Conclusions: In a population-based cohort of North American women, menstrual irregularity, increased cycle and bleeds lengths, and heavier menstrual bleeds were associated with self-reported hirsutism. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between adiposity, physical activity (PA), and fecundability.Design: Prospective cohort study.Setting: Not applicable.Patient(s): A total of 2,062 female pregnancy planners from the United States and Canada who were enrolled during the preconception period.Intervention(s): None.Main Outcome Measure(s): Self-reported pregnancy. Fecundability ratios (FRs) and 95% confidence intervals (CIs) were estimated using proportional probabilities models that adjusted for potential confounders.Result(s): Relative to body mass index (BMI) 18.5-24 kg/m(2), FRs for BMI <18.5, 25-29, 30-34, 35-39, 40-44, and ≥45 kg/m(2) were 1.05 (95% CI 0.76-1.46), 1.01 (95% CI 0.89-1.15), 0.98 (95% CI 0.82-1.18), 0.78 (95% CI 0.60-1.02), 0.61 (95% CI 0.42-0.88), and 0.42 (95% CI 0.23-0.76), respectively. Reduced fecundability was observed among women with the largest waist-to-hip ratios (≥0.85 vs. <0.75; FR = 0.87, 95% CI 0.74-1.01) and waist circumferences (≥36 vs. <26 inches [≥90 vs. <66 cm]; FR = 0.80, 95% CI 0.59-1.01). Tendency to gain weight in the chest/shoulders (FR = 0.63, 95% CI 0.36-1.08) and waist/stomach (FR = 0.90, 95% CI 0.79-1.02), relative to hips/thighs, was associated with lower fecundability. Moderate PA was associated with increased fecundability (≥5 vs. <1 h/wk; FR = 1.26, 95% CI 0.96-1.65), but there was no dose-response relation. Among overweight/obese women (BMI ≥25 kg/m(2)), fecundability was 27% higher for vigorous PA of ≥5 versus <1 h/wk (95% CI 1.02-1.57).Conclusion(s): Various measures of overall and central adiposity were associated with decreased fertility among pregnancy planners. Vigorous PA was associated with improved fertility among overweight and obese women only; moderate PA was associated with improved fertility among all women. [ABSTRACT FROM AUTHOR]

Background We launched the Boston University Pregnancy Study Online ( PRESTO) to assess the feasibility of carrying out an Internet-based preconception cohort study in the US and Canada. Methods We recruited female participants age 21-45 and their male partners through Internet advertisements, word of mouth, and flyers. Female participants were randomised with 50% probability to receive a subscription to FertilityFriend.com ( FF), a web-based programme that collects real-time data on menstrual characteristics. We compared recruitment methods within PRESTO, assessed the cost-efficiency of PRESTO relative to its Danish counterpart ( Snart- Gravid), and validated retrospectively reported date of last menstrual period ( LMP) against the FF data. Results After 99 weeks of recruitment (2013-15), 2421 women enrolled; 1384 (57%) invited their male partners to participate, of whom 693 (50%) enrolled. Baseline characteristics were balanced across randomisation groups. Cohort retention was similar among those randomised vs. not randomised to FF (84% vs. 81%). At study enrolment, 56%, 22%, and 22% couples had been trying to conceive for <3, 3-5, and ≥6 months, respectively. The cost per subject enrolled was $146 (2013 US$), which was similar to our companion Danish study and half that of a traditional cohort study. Among FF users who conceived, >97% reported their LMP on the PRESTO questionnaire within 1 day of the LMP recorded via FF. Conclusions Use of the Internet as a method of recruitment and follow-up in a North American preconception cohort study was feasible and cost-effective. [ABSTRACT FROM AUTHOR]

• Phthalates widely detected among a cohort of reproductive-aged Black women. • Biomarkers generally showed weak-to-moderate inverse associations with UL incidence. • Inverse associations stronger among women with BMI ≥ 30 kg/m2 for specific phthalates. • Little evidence of effect of the phthalate biomarkers mixture on UL incidence. Numerous studies suggest that some phthalates have adverse reproductive effects. However, literature on the association between phthalates and incidence of uterine leiomyomata (UL) is limited and inconsistent, with no existing prospective studies. We examined the association of urinary concentrations of phthalate and phthalate alternative biomarkers with UL incidence. We conducted a case-cohort analysis within a subgroup of 754 participants in the Study of the Environment, Lifestyle, and Fibroids (SELF), a prospective cohort of premenopausal Black women aged 23–35 years who were recruited during 2010–2012. We quantified fourteen phthalates and two phthalate alternative [1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH)] biomarkers in urine collected at baseline, 20 months, and 40 months. Transvaginal ultrasounds identified UL at baseline and every 20 months during 60 months of follow-up. We evaluated the individual biomarkers, molar sum of di(2-ethylhexyl) phthalate [ΣDEHP] and potency-weighted sum of anti-androgenic [WΣAA] biomarkers. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between biomarkers and UL incidence. We then used quantile g-computation to examine joint associations of multiple phthalate biomarkers with UL incidence. Most individual biomarkers showed weak-to-moderate inverse associations with UL incidence. HRs comparing highest vs. lowest quartiles of mono-isobutyl phthalate (MiBP) and mono-hydroxyisobutyl phthalate (MHiBP) concentrations were 0.63 (95% CI: 0.40, 1.01) and 0.61 (95% CI: 0.38, 0.96), respectively. Inverse associations for specific phthalates were stronger among women with BMI ≥ 30 kg/m2. HRs comparing detectable vs. nondetectable concentrations of DINCH biomarkers were 0.92 (95% CI: 0.62, 1.35) for cyclohexane-1,2-dicarboxylic acid mono hydroxyisononyl ester (MHNCH) and 0.68 (95% CI: 0.38, 1.18) for cyclohexane-1,2-dicarboxylic acid mono carboxyisoocytl ester (MCOCH). For the DEHP metabolite of mono(2-ethylhexyl) phthalate (MEHP), we observed weak-to-moderate positive associations. HRs comparing highest vs. lowest quartiles for MEHP and ΣDEHP were 1.29 (95% CI: 0.82, 2.06) and 0.96 (95% CI: 0.61, 1.50), respectively. In the mixtures analysis, the HR for a joint quartile increase in phthalate biomarker concentrations was 0.90 (95% CI: 0.73, 1.08). In this prospective ultrasound study of reproductive-aged Black women, urinary concentrations of phthalate and DINCH biomarkers were not appreciably associated with higher risk of UL, either individually or jointly. [ABSTRACT FROM AUTHOR]