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Increased fossil fuel usage and extreme climate change events have led to global increases in greenhouse gases and particulate matter with 99% of the world's population now breathing polluted air that exceeds the World Health Organization's recommended limits. Pregnant women and neonates with exposure to high levels of air pollutants are at increased risk of adverse health outcomes such as maternal hypertensive disorders, postpartum depression, placental abruption, low birth weight, preterm birth, infant mortality, and adverse lung and respiratory effects. While the exact mechanism by which air pollution exerts adverse health effects is unknown, oxidative stress as well as epigenetic and immune mechanisms are thought to play roles. Comprehensive, global efforts are urgently required to tackle the health challenges posed by air pollution through policies and action for reducing air pollution as well as finding ways to protect the health of vulnerable populations in the face of increasing air pollution. [ABSTRACT FROM AUTHOR]

Background: Use of menstrual tracking data to understand abnormal bleeding patterns has been limited because of lack of incorporation of key demographic and health characteristics and confirmation of menstrual tracking accuracy.Objective: This study aimed to identify abnormal uterine bleeding patterns and their prevalence and confirm existing and expected associations between abnormal uterine bleeding patterns, demographics, and medical conditions.Study Design: Apple Women's Health Study participants from November 2019 through July 2021 who contributed menstrual tracking data and did not report pregnancy, lactation, use of hormones, or menopause were included in the analysis. Four abnormal uterine bleeding patterns were evaluated: irregular menses, infrequent menses, prolonged menses, and irregular intermenstrual bleeding (spotting). Monthly tracking confirmation using survey responses was used to exclude inaccurate or incomplete digital records. We investigated the prevalence of abnormal uterine bleeding stratified by demographic characteristics and used logistic regression to evaluate the relationship of abnormal uterine bleeding to a number of self-reported medical conditions.Results: There were 18,875 participants who met inclusion criteria, with a mean age of 33 (standard deviation, 8.2) years, mean body mass index of 29.3 (standard deviation, 8.0), and with 68.9% (95% confidence interval, 68.2-69.5) identifying as White, non-Hispanic. Abnormal uterine bleeding was found in 16.4% of participants (n=3103; 95% confidence interval, 15.9-17.0) after accurate tracking was confirmed; 2.9% had irregular menses (95% confidence interval, 2.7-3.1), 8.4% had infrequent menses (95% confidence interval, 8.0-8.8), 2.3% had prolonged menses (95% confidence interval, 2.1-2.5), and 6.1% had spotting (95% confidence interval, 5.7-6.4). Black participants had 33% higher prevalence (prevalence ratio, 1.33; 95% confidence interval, 1.09-1.61) of infrequent menses compared with White, non-Hispanic participants after controlling for age and body mass index. The prevalence of infrequent menses was increased in class 1, 2, and 3 obesity (class 1: body mass index, 30-34.9; prevalence ratio, 1.31; 95% confidence interval, 1.13-1.52; class 2: body mass index, 35-39.9; prevalence ratio, 1.25; 95% confidence interval, 1.05-1.49; class 3: body mass index, >40; prevalence ratio, 1.51; 95% confidence interval, 1.21-1.88) after controlling for age and race/ethnicity. Those with class 3 obesity had 18% higher prevalence of abnormal uterine bleeding compared with healthy-weight participants (prevalence ratio, 1.18; 95% confidence interval, 1.02-1.38). Participants with polycystic ovary syndrome had 19% higher prevalence of abnormal uterine bleeding compared with participants without this condition (prevalence ratio, 1.19; 95% confidence interval, 1.08-1.31). Participants with hyperthyroidism (prevalence ratio, 1.34; 95% confidence interval, 1.13-1.59) and hypothyroidism (prevalence ratio, 1.17; 95% confidence interval, 1.05-1.31) had a higher prevalence of abnormal uterine bleeding, as did those reporting endometriosis (prevalence ratio, 1.28; 95% confidence interval, 1.12-1.45), cervical dysplasia (prevalence ratio, 1.20; 95% confidence interval, 1.03-1.39), and fibroids (prevalence ratio, 1.14; 95% confidence interval, 1.00-1.30).Conclusion: In this cohort, abnormal uterine bleeding was present in 16.4% of those with confirmed menstrual tracking. Black or obese participants had increased prevalence of abnormal uterine bleeding. Participants reporting conditions such as polycystic ovary syndrome, thyroid disease, endometriosis, and cervical dysplasia had a higher prevalence of abnormal uterine bleeding. [ABSTRACT FROM AUTHOR]

Background Tetrachloroethylene (PCE) is an organic lipophilic solvent with possible neuroendocrine toxicity. The objective of this study was to determine the association of prenatal and early childhood exposure to PCE-contaminated drinking water and development of adult-onset Polycystic Ovary Syndrome (PCOS), endometriosis, difficulty conceiving and miscarriage. Methods Five-hundred exposed and 331 unexposed female participants born between 1969 and 1983 completed questionnaires on demographic and lifestyle characteristics, and reproductive disorders. Residential locations from the prenatal period through five years of age were used to estimate early life PCE exposure with water modeling software. Results For any early life exposure to PCE, the adjusted risk ratio for PCOS was 0.9 (95% CI: 0.5-1.6). No statistically significant associations were observed for increasing levels of exposure with PCOS or the other reproductive disorders. Conclusion No meaningful associations were found among adult women with early life exposure to PCE-contaminated drinking water and adult-onset reproductive disorders. [ABSTRACT FROM AUTHOR]

Cosmetics contain a vast number of chemicals, most of which are not under the regulatory purview of the Food and Drug Administration. Only a few of these chemicals have been evaluated for potential deleterious health impact: parabens, phthalates, polycyclic aromatic hydrocarbons, and siloxanes. A review of the ingredients in the best-selling and top-rated products of the top beauty brands in the world, as well as a review of highlighted chemicals by nonprofit environmental organizations, reveals 11 chemicals and chemical families of concern: butylated hydroxyanisole/butylated hydroxytoluene, coal tar dyes, diethanolamine, formaldehyde-releasing preservatives, parabens, phthalates, 1,4-dioxane, polycyclic aromatic hydrocarbons, siloxanes, talc/asbestos, and triclosan. Age at menopause can be affected by a variety of mechanisms, including endocrine disruption, failure of DNA repair, oxidative stress, shortened telomere length, and ovarian toxicity. There is a lack of available studies to make a conclusion regarding cosmetics use and age at menopause. What little data there are suggest that future studies are warranted. Women with chronic and consistent use of cosmetics across their lifespan may be a population of concern. More research is required to better elucidate the relationship and time windows of vulnerability and the effects of mixtures and combinations of products on ovarian health. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that emergent events may affect pregnancy planning decisions. However, few have investigated the effect of factors related to the COVID-19 pandemic on pregnancy planning, measured by attempting conception, and how attempting conception status may differ by individual-level factors, such as social status or educational level.Objective: This study aimed to examine the effects of factors related to the COVID-19 pandemic, until March 2021, on attempting conception status and to assess the effect measure modification by educational level and subjective social status.Study Design: We conducted a longitudinal analysis within a subgroup of 21,616 participants in the Apple Women's Health Study who enrolled from November 2019 to March 2021, who met the inclusion criteria, and who responded to the monthly status menstrual update question on attempting conception status (yes or no). Participants reporting hysterectomy, pregnancy, lactation, or menopause were excluded. We used generalized estimating equation methodology to fit logistic regression models that estimate odds ratios and 95% confidence intervals for the association between the proportion of participants attempting conception and the month of response (compared with a prepandemic reference month of February 2020) while accounting for longitudinal correlation and adjusting for age, race and ethnicity, and marital status. We stratified the analysis by social status and educational level.Results: We observed a trend of reduced odds of attempting conception, with an 18% reduction in the odds of attempting conception in August 2020 and October 2020 compared with the prepandemic month of February 2020 (August odds ratio: 0.82 [95% confidence interval, 0.70-0.97]; October odds ratio: 0.82 [95% confidence interval, 0.69-0.97). The participants with lower educational level (no college education) experienced a sustained reduction in the odds of attempting to conceive from June 2020 to March 2021 compared with February 2020, with up to a 24% reduction in the odds of attempting to conceive in October 2020 (odds ratio, 0.76; 95% confidence interval, 0.59-0.96). Among participants that were college educated, we observed an initial reduction in the odds of attempting to conceive starting in July 2020 (odds ratio 0.73; 95% confidence interval, 0.54-0.99) that returned near prepandemic odds. Moreover, we observed a reduction in the odds of attempting to conceive among those with low subjective social status, with a decline in the odds of attempting to conceive beginning in July 2020 (odds ratio, 0.83; 95% confidence interval, 0.63-1.10) and continuing until March 2021 (odds ratio, 0.79; 95% confidence interval, 0.59-1.06), with the greatest reduction in odds in October 2020 (odds ratio, 0.67; 95% confidence interval, 0.50-0.91).Conclusion: Among women in the Apple Women's Health Study cohort, our findings suggested a reduction in the odds of attempting to conceive during the COVID-19 pandemic, until March 2021, particularly among women of lower educational level and lower perceived social status. [ABSTRACT FROM AUTHOR]

Background: Prospective longitudinal cohorts assessing women's health and gynecologic conditions have historically been limited.Objective: The Apple Women's Health Study was designed to gain a deeper understanding of the relationship among menstrual cycles, health, and behavior. This paper describes the design and methods of the ongoing Apple Women's Health Study and provides the demographic characteristics of the first 10,000 participants.Study Design: This was a mobile-application-based longitudinal cohort study involving survey and sensor-based data. We collected the data from 10,000 participants who responded to the demographics survey on enrollment between November 14, 2019 and May 20, 2020. The participants were asked to complete a monthly follow-up through November 2020. The eligibility included installed Apple Research app on their iPhone with iOS version 13.2 or later, were living in the United States, being of age greater than 18 years (19 in Alabama and Nebraska, 21 years old in Puerto Rico), were comfortable in communicating in written and spoken English, were the sole user of an iCloud account or iPhone, and were willing to provide consent to participate in the study.Results: The mean age at enrollment was 33.6 years old (±standard deviation, 10.3). The race and ethnicity was representative of the US population (69% White and Non-Hispanic [6910/10,000]), whereas 51% (5089/10,000) had a college education or above. The participant geographic distribution included all the US states and Puerto Rico. Seventy-two percent (7223/10,000) reported the use of an Apple Watch, and 24.4% (2438/10,000) consented to sensor-based data collection. For this cohort, 38% (3490/9238) did not respond to the Monthly Survey: Menstrual Update after enrollment. At the 6-month follow-up, there was a 35% (3099/8972) response rate to the Monthly Survey: Menstrual Update. 82.7% (8266/10,000) of the initial cohort and 95.1% (2948/3099) of the participants who responded to month 6 of the Monthly Survey: Menstrual Update tracked at least 1 menstrual cycle via HealthKit. The participants tracked their menstrual bleeding days for an average of 4.44 (25%-75%; range, 3-6) calendar months during the study period. Non-White participants were slightly more likely to drop out than White participants; those remaining at 6 months were otherwise similar in demographic characteristics to the original enrollment group.Conclusion: The first 10,000 participants of the Apple Women's Health Study were recruited via the Research app and were diverse in race and ethnicity, educational attainment, and economic status, despite all using an Apple iPhone. Future studies within this cohort incorporating this high-dimensional data may facilitate discovery in women's health in exposure outcome relationships and population-level trends among iPhone users. Retention efforts centered around education, communication, and engagement will be utilized to improve the survey response rates, such as the study update feature. [ABSTRACT FROM AUTHOR]

There is a lack of data regarding potential exposure of gametes to bisphenol A during IVF. Detectable concentrations of bisphenol A were not found in commonly used IVF plastic culture dishes, suction tubing or growth media under normal-use conditions. [ABSTRACT FROM AUTHOR]

To evaluate the association between the urinary benzophenone-3 concentrations and measures of ovarian reserve (OR) among women in the Environment and Reproductive Health study seeking fertility treatment at Massachusetts General Hospital (MGH) in Boston, Massachusetts. Prospective cohort study. MGH infertility clinic in Boston, Massachusetts. Women in the Environment and Reproductive Health cohort seeking fertility treatment. Women contributed spot urine samples prior to assessment of OR outcomes that were analyzed for benzophenone-3 concentrations. Antral follicle count (AFC) and day 3 follicle-stimulating hormone (FSH) levels were evaluated as part of standard infertility workups during unstimulated menstrual cycles. Quasi-Poisson and linear regression models were used to evaluate the association of the specific gravity–adjusted urinary benzophenone-3 concentrations with AFC and FSH, with adjustment for age and physical activity. In the secondary analyses, models were stratified by age. This study included 142 women (mean age ± standard deviation, 36.1 ± 4.6 years; range, 22–45 years) enrolled between 2009 and 2017 with both urinary benzophenone-3 and AFC measurements and 57 women with benzophenone-3 and FSH measurements. Most women were White (78%) and highly educated (49% with a graduate degree). Women contributed a mean of 2.7 urine samples (range, 1–10), with 37% contributing ≥2 samples. Benzophenone-3 was detected in 98% of samples. The geometric mean specific gravity–corrected urinary benzophenone-3 concentration was 85.9 μg/L (geometric standard deviation, 6.2). There were no associations of benzophenone-3 with AFC and day 3 FSH in the full cohort. In stratified models, a 1-unit increase in the log geometric mean benzophenone-3 concentration was associated with a 0.91 (95% confidence interval, 0.86–0.97) times lower AFC among women aged ≤35 years and an increase in the FSH concentration of 0.73 (95% confidence interval, 0.12–1.34) IU/L among women aged >35 years. In the main models, urinary benzophenone-3 was not associated with OR. However, younger patients may be vulnerable to the potential effects of benzophenone-3 on AFC. Further research is warranted. [ABSTRACT FROM AUTHOR]

Evidence has shown associations between air pollution and traffic-related exposure with accelerated aging, but no study to date has linked the exposure with age at natural menopause, an important indicator of reproductive aging. In this study, we sought to examine the associations of residential exposure to ambient particulate matter (PM) and distance to major roadways with age at natural menopause in the Nurses' Health Study II (NHS II), a large, prospective female cohort in US. A total of 105,996 premenopausal participants in NHS II were included at age 40 and followed through 2015. Time-varying residential exposures to PM 10 , PM 2.5-10 , and PM 2.5 and distance to roads was estimated. We calculated hazard ratios (HR) and 95% confidence intervals (CIs) for natural menopause using Cox proportional hazard models adjusting for potential confounders and predictors of age at menopause. We also examined effect modification by region, smoking, body mass, physical activity, menstrual cycle length, and population density. There were 64,340 reports of natural menopause throughout 1,059,229 person-years of follow-up. In fully adjusted models, a 10 μg/m3 increase in the cumulative average exposure to PM 10 (HR: 1.02, 95% CI: 1.00, 1.04), PM 2.5-10 (HR: 1.03, 95% CI: 1.00, 1.05), and PM 2.5 (HR: 1.03, 95% CI: 1.00, 1.06) and living within 50 m to a major road at age 40 (HR: 1.03, 95%CI: 1.00, 1.06) were associated with slightly earlier menopause. No statistically significant effect modification was found, although the associations of PM were slightly stronger for women who lived in the West and for never smokers. To conclude, we found exposure to ambient PM and traffic in midlife was associated with slightly earlier onset of natural menopause. Our results support previous evidence that exposure to air pollution and traffic may accelerate reproductive aging. Image 1 • Limited evidence on air pollution and traffic with reproductive aging. • We examined associations of these exposure and menopausal age in a large cohort. • Women with higher residential PM in midlife had slightly earlier menopause. • Women who lived closer to roads in early midlife had slightly earlier menopause. • Our finding supported air pollution and traffic may accelerate reproductive aging. [ABSTRACT FROM AUTHOR]

The association between educational level and cycle outcomes was quantified by applying multivariable logistic and linear regression within a prospective cohort of 2,569 women commencing their first in vitro fertilization (IVF) cycle. Although a woman’s educational attainment was not associated with the likelihood of implantation failure, chemical pregnancy, spontaneous abortion, or live birth, the odds of cycle cancellation before egg retrieval were 40% lower among those with an college degree and 48% lower among those with graduate school attendance compared with women who had no college degree, suggesting that educational attainment is inversely associated with the likelihood of cycle cancellation. [Copyright &y& Elsevier]

[Display omitted] The menopausal transition involves significant sex hormone changes. Environmental chemicals, such as urinary phthalate metabolites, are associated with sex hormone levels in cross-sectional studies. Few studies have assessed longitudinal associations between urinary phthalate metabolite concentrations and sex hormone levels during menopausal transition. Pre- and perimenopausal women from the Midlife Women's Health Study (MWHS) (n = 751) contributed data at up to 4 annual study visits. We quantified 9 individual urinary phthalate metabolites and 5 summary measures (e.g., phthalates in plastics (∑Plastic)), using pooled annual urine samples. We measured serum estradiol, testosterone, and progesterone collected at each study visit, unrelated to menstrual cycling. Linear mixed-effects models and hierarchical Bayesian kernel machine regression analyses evaluated adjusted associations between individual and phthalate mixtures with sex steroid hormones longitudinally. We observed associations between increased concentrations of certain phthalate metabolites and lower testosterone and higher sub-ovulatory progesterone levels, e.g., doubling of monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), di-2-ethylhexyl phthalate (∑DEHP) metabolites, ∑Plastic, and ∑Phthalates concentrations were associated with lower testosterone (e.g., for ∑DEHP: −4.51%; 95% CI: −6.72%, −2.26%). For each doubling of MEP, certain DEHP metabolites, and summary measures, we observed higher mean sub-ovulatory progesterone (e.g., ∑AA (metabolites with anti-androgenic activity): 6.88%; 95% CI: 1.94%, 12.1%). Higher levels of the overall time-varying phthalate mixture were associated with lower estradiol and higher progesterone levels, especially for 2nd year exposures. Phthalates were longitudinally associated with sex hormone levels during the menopausal transition. Future research should assess such associations and potential health impacts during this understudied period. [ABSTRACT FROM AUTHOR]

Objective: To determine the dose-dependent effect of delta-9-tetrahydrocannabinol (THC) exposure on male testes and reproductive health in a nonhuman primate model.Design: Research animal study.Setting: Research institute.Animal(s): Adult male rhesus macaques 8-10 years of age (n = 6).Intervention(s): Daily edible THC at medically and recreationally relevant doses.Main Outcome Measure(s): Testicular volume and epididymal head width, serum levels of inhibin B, albumin, total testosterone, prolactin, follicle-stimulating hormone, estradiol, and luteinizing hormone; semen volume; and sperm motility, morphology, and concentration.Result(s): For each 1 mg/7 kg/day increase in THC dosing, there was a marked loss in total bilateral testicular volume of 11.8 cm3 (95% confidence interval [CI]: 8.3-15.4). In total, average bilateral testicular volume decreased by 58%. Significant dose-response decreases in mean total testosterone level by 1.49 ng/mL (95% CI: 0.83-2.15) and in estradiol level by 3.8 pg/mL (95% CI: 2.2-5.4) were observed, but significant increases in the levels of follicle-stimulating hormone by 0.06 ng/mL (95% CI: 0.02-0.10), luteinizing hormone by 0.16 ng/mL (95% CI: 0.08-0.25), and prolactin by 7.4 ng/mL (95% CI: 3.4-11.3) were observed. There were no statistically significant changes in semen parameters.Conclusion(s): In rhesus macaques, chronic exposure to THC resulted in significant dose-response testicular atrophy, increased serum gonadotropin levels, and decreased serum sex steroids, suggestive of primary testicular failure. Further studies are needed to determine if reversal of these observed adverse effects would occur if THC was discontinued and for validation of thefindings in a human cohort. [ABSTRACT FROM AUTHOR]

Objective: To compare the effect of preoperative intravenous (IV) acetaminophen versus oral (PO) acetaminophen or placebo on postoperative pain scores and the time to discharge in women undergoing oocyte retrieval.Design: Randomized, double-blind, placebo-controlled trial.Setting: Single academic fertility center.Patient(s): Women aged 18-43 years undergoing oocyte retrieval.Intervention(s): Randomization to preoperative 1,000 mg IV acetaminophen and PO placebo (group A), IV placebo and 1,000 mg PO acetaminophen (group B), or IV and PO placebo (group C) MAIN OUTCOME MEASURE(S): Difference in patient-reported postoperative visual analog scale pain scores from baseline and the time to discharge.Result(s): Of the 159 women who completed the study, there were no differences in the mean postoperative pain score differences or the time to discharge. Although not statistically significant, the mean postoperative opioid dose requirement in group A was lower than that in groups B and C (0.24 vs. 0.59 vs. 0.58 mg IV morphine equivalents, respectively) due to fewer women in group A requiring rescue pain medication (8% vs. 19% vs. 15%, respectively). Group A also reported less constipation when compared with groups B and C (19% vs. 33% vs. 40%, respectively). The rates of postoperative nausea were similar, and there were no differences in embryology or early pregnancy outcomes between the study groups.Conclusion(s): Preoperative IV acetaminophen for women undergoing oocyte retrieval did not reduce postoperative pain scores or shorten the time to discharge when compared with PO acetaminophen or placebo and, thus, cannot currently be recommended routinely in this patient population.Clinical Trial Registration Number: NCT03073980. [ABSTRACT FROM AUTHOR]

[Display omitted] • PFOS was associated with higher parameters of gestational BP trajectories. • Positive associations were stronger in participants with parity ≥ 1. Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases risk of high blood pressure (BP) during pregnancy. Prior studies did not examine associations with BP trajectory parameters (i.e., overall magnitude and velocity) during pregnancy, which is linked to adverse pregnancy outcomes. To estimate associations of multiple plasma PFAS in early pregnancy with BP trajectory parameters across the second and third trimesters. To assess potential effect modification by maternal age and parity. In 1297 individuals, we quantified six PFAS in plasma collected during early pregnancy (median gestational age: 9.4 weeks). We abstracted from medical records systolic BP (SBP) and diastolic BP (DBP) measurements, recorded from 12 weeks gestation until delivery. BP trajectory parameters were estimated via Super Imposition by Translation and Rotation modeling. Subsequently, Bayesian Kernel Machine Regression (BKMR) was employed to estimate individual and joint associations of PFAS concentrations with trajectory parameters – adjusting for maternal age, race/ethnicity, pre-pregnancy body mass index, income, parity, smoking status, and seafood intake. We evaluated effect modification by age at enrollment and parity. We collected a median of 13 BP measurements per participant. In BKMR, higher concentration of perfluorooctane sulfonate (PFOS) was independently associated with higher magnitude of overall SBP and DBP trajectories (i.e., upward shift of trajectories) and faster SBP trajectory velocity, holding all other PFAS at their medians. In stratified BKMR analyses, participants with ≥ 1 live birth had more pronounced positive associations between PFOS and SBP velocity, DBP magnitude, and DBP velocity – compared to nulliparous participants. We did not observe significant associations between concentrations of the overall PFAS mixture and either magnitude or velocity of the BP trajectories. Early pregnancy plasma PFOS concentrations were associated with altered BP trajectory in pregnancy, which may impact future cardiovascular health of the mother. [ABSTRACT FROM AUTHOR]

• Digital cohort of 125,104 menstrual cycles from 17,427 participants within the US. • Modest seasonal variation of menstrual cycle length from June 2020 to July 2022. • Shorter cycles (<1/5 day) in May–Aug and Sept–Dec compared to Jan–April. • Younger participants <35°N and >40°N with PCOS had strongest seasonal trends. • No seasonal patterns in cycle lengths were found for participants above age 40. [ABSTRACT FROM AUTHOR]

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

• Exposure to phthalates has previously been linked to worsened IVF outcomes. • Increased urinary phthalates were associated with decreased follicular fluid AMH. • Phthalate exposure may accelerate follicular recruitment, lowering ovarian reserve. Exposure to phthalates, endocrine-disrupting chemicals commonly used as plasticizers and in consumer products, has been associated with infertility and premature ovarian failure. Our objective was to investigate whether urinary phthalate metabolite concentrations were associated with pre-ovulatory follicular fluid (FF) anti-müllerian hormone (AMH) concentrations in women undergoing fertility treatment. This cross-sectional analysis included 138 women with urinary phthalate data available in the Environment and Reproductive Health (EARTH) Study (2010–2016) in whom FF AMH concentrations were quantified using a sandwich enzyme-linked immunosorbent assay (ELISA). We also quantified 8 phthalate metabolite concentrations using tandem mass spectrometry in 1–2 urine samples per cycle (total 331 urines) and calculated the cycle-specific geometric mean for each metabolite. We applied cluster-weighted generalized estimating equation models (CWGEE) to evaluate the associations of tertiles of urinary phthalate metabolite concentrations with log-transformed FF AMH concentrations adjusting for potential confounders. Study participants had median age of 34.0 years (IQR 32.0, 37.0), 83% were white, and median BMI of 23.1 kg/m2 (IQR 21.2, 26.1). The following stimulation protocols were used: luteal phase agonist (70%), antagonist (14%), or flare (16%). Urinary concentrations of select phthalate metabolites were negatively associated with FF AMH. For example, women whose urinary mEOHP was in the lowest tertile (range 0.30–4.04 ng/ml) had an adjusted mean FF AMH of 0.72 ng/mL (95% CI = 0.36, 1.44), compared to women in the highest tertile (range 9.90–235), who had an adjusted mean of 0.24 ng/mL (95% CI = 0.12–0.48, p < 0.05). The negative association between urinary concentrations of certain phthalate metabolites with FF AMH concentrations may have implications for antral follicle recruitment and fertility treatment outcomes. [ABSTRACT FROM AUTHOR]

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]