Early Life Anti-Müllerian Hormone Trajectories in Infant Girls.

BACKGROUND: Minipuberty is a period of increased reproductive axis activity in infancy, but the importance of this period is not well understood, especially in girls. Previous studies reported a peak in hormone concentrations at 3 to 4 months old. Our objective is to describe anti-Müllerian hormone (AMH) trajectories in the context of other minipuberty factors among healthy infant girls using longitudinal measures of AMH. METHODS: The Infant Feeding and Early Development study is a longitudinal cohort study of healthy infants, recruited from hospitals in the Philadelphia area during 2010 to 2013. We measured AMH in 153 girls who contributed 1366 serum samples across 11 study visits over 36 weeks. We also measured follicle stimulating hormone (FSH), estradiol, and ovarian characteristics. We used latent class mixed effects models to cluster trajectories of AMH concentration with age. Using linear mixed models, we estimated FSH and ovarian characteristic trajectories separately by AMH cluster. RESULTS: We classified infants into four clusters that represent patterns of AMH that were high and decreasing (decreasing), had a peak around 12 weeks or 20 weeks (early peak and middle peak), or were consistently low (low). Infants in these clusters differed in their FSH trajectories, timing of estradiol production, and ovarian characteristics. CONCLUSIONS: The AMH clusters identified suggest variation in the timing and the magnitude of the minipuberty response in infant girls. The decreasing and low clusters have not been described previously and should be further evaluated to determine whether they represent an opportunity for the early identification of later reproductive conditions.

Outdoor air pollution and anti-Müllerian hormone concentrations in the Sister Study.

BACKGROUND: Anti-Müllerian hormone (AMH) concentrations are a marker of ovarian reserve and are indicative of a woman's reproductive lifespan. Exposure to tobacco smoke has been associated with lower AMH concentrations; however, less is known about the association between ambient air pollution and ovarian reserve. METHODS: For 883 premenopausal Sister Study participants recruited between 2003 and 2009 in the United States, adult residential annual average concentrations of PM2.5, PM10, and NO2 were estimated using validated universal kriging models incorporating land-use regression. We estimated the distance in meters to the nearest major road for both adult enrollment and childhood residences. Serum AMH was measured using an ultrasensitive ELISA assay. Samples with AMH concentrations below the detection limit were analyzed using a picoAMH ELISA assay. Multivariable-adjusted linear regression was used to estimate the percent change in AMH in relation to ambient residential air pollution, categorized in quartiles and per interquartile range increase, and distance to a major roadway. RESULTS: Overall, we observed little to no evidence of associations between AMH and air pollution concentrations or proximity to roadways. Women in the highest quartile of NO2 exposure, a traffic-related pollutant, had higher estimated AMH concentrations (Q4 vs. Q1, 42.9%; 95% CI = -3.4, 111.4) compared with the lowest quartile. However, lower mean AMH concentrations were observed for women living closer to a major roadway (<50 m to nearest roadway vs. ≥200 m = -32.9%; 95% CI = -56.1, 2.6). CONCLUSIONS: We saw little consistent evidence to support an association between outdoor air pollution and diminished ovarian reserve in US women ages 35-54.

Prevalence of Hirsutism Among Reproductive-Aged African American Women.

Background: Hirsutism is the most common clinical symptom of hyperandrogenism, but racial and ethnic-specific thresholds have not been established. Our objective was to characterize hirsutism using self-report of hair growth in a large sample of African American women. Materials and Methods: The Study of Environment, Lifestyle, and Fibroids is a prospective community-based cohort study of African American women (23-34 at recruitment). A total of 1568 participants received the modified Ferriman-Gallwey (mFG) pictorial assessment and were asked if they were ever bothered by excess hair. We estimated the prevalence of hirsutism (mFG score ≥8) and associations of acne, polycystic ovary syndrome (PCOS), and menstrual cycle characteristics with hirsutism. We also explored hirsutism defined by the 95th percentile of scores in our cohort (mFG = 11) and a newly recommended criterion, mFG = 4. Results: We could determine hirsutism status in 1556 women. Thirty-seven percent reported being bothered by excess hair, and 10% met the mFG criterion for hirsutism. History of severe facial acne was positively associated with hirsutism (prevalence ratio: 1.90; 95% confidence interval [CI]: 1.30-2.76), as was physician-diagnosed PCOS (2.22, 95% CI: 1.30-3.81). Women with irregular menstrual cycles were also more likely to report hirsutism (1.78, 95% CI: 1.00-3.18). Results were similar using mFG ≥11 and attenuated using mFG ≥4. Conclusions: Hirsutism prevalence was 10% in this community sample of African American women and was associated with PCOS, severe acne, and irregular menstrual cycles suggesting this represented hirsutism caused by hyperandrogenism. Ethnically diverse, population-based studies assessing the association between mFG score and androgen levels are needed to better understand the hirsutism threshold as a clinical marker of hyperandrogenism.

Douching or Perineal Talc Use and Prevalent Fibroids in Young African American Women.

Background: Black women are at an increased risk of developing fibroids, but the cause is unclear. Douching and perineal talc use are common lifestyle exposures among Black women, and may be risk factors for fibroid development. Materials and Methods: This cross-sectional study consisted of Black women 23-35 years of age in the metropolitan Detroit area (n = 1693) without prior diagnoses of fibroids and intact uteri. Main exposures were ever douching (yes/no) and any perineal talc use (ever/never). Main outcomes were prevalent fibroids at baseline (yes/no) and total fibroid volume at baseline (no fibroids/

Association of urinary concentrations of early pregnancy phthalate metabolites and bisphenol A with length of gestation.

BACKGROUND: Environmental exposure to phthalates and bisphenol A (BPA) may have endocrine disrupting effects that alter length of gestation. We assessed the association between the urinary concentrations of 11 phthalate metabolites and BPA with length of gestation in a cohort of women followed from before conception with daily 1st-morning urinary hormone measures that identified day of implantation. METHODS: Pre-implantation and post-implantation urinary phthalate metabolites and BPA concentrations were measured in pooled urine samples designed to limit single-measure variability due to the likely episodic nature of these exposures and the short half-life of these compounds. We estimated associations between these exposure biomarkers early in pregnancy with length of gestation from implantation to spontaneous birth. Cox proportional hazards models were used to estimate the hazard of birth among 125 naturally-conceived, singleton live births with censoring for medical interventions that artificially shortened pregnancy. RESULTS: Higher concentrations of mono (2-ethyl-5-hydroxyhexyl) phthalate (a metabolite of di (2-ethylhexyl) phthalate (DEHP)) during the pre-implantation window were associated with reduced probability of birth, i.e., longer gestations (hazard ratio (HR): 0.55, 95% CI: 0.35, 0.86; p = 0.01). The HR for the molar sum of the four DEHP metabolites measured showed a similar association (HR: 0.67, 95% CI: 0.43, 1.05). Higher concentrations of mono (3-carboxypropyl) phthalate (MCPP), a non-specific metabolite of several high molecular-weight phthalates, measured post-implantation were associated with increased risk of earlier birth, i.e. shorter length of gestation, HR: 1.59, CI: 1.02, 2.49. CONCLUSIONS: Early gestational exposure to DEHP and possibly other high-molecular weight phthalates, (as reflected by urinary MCPP concentrations) may influence the length of pregnancy. Such effects could have consequences for neonatal and maternal health.

Association of urinary concentrations of phthalate metabolites and bisphenol A with early pregnancy endpoints.

BACKGROUND: Phthalates and bisphenol A (BPA) are environmental contaminants that may affect early embryonic development. OBJECTIVE: To assess the association between phthalate metabolites and BPA with early pregnancy endpoints in a cohort of women followed from before conception. METHODS: We quantified 11 phthalate metabolites and BPA in 137 conception cycles from naturally conceived clinical pregnancies. Phthalate metabolites and BPA concentrations were measured in a pooled sample of three daily morning urine specimens. Daily urinary hormone measurements had previously been used to define ovulation, implantation, and corpus luteum rescue. We assessed associations between conception cycle exposures (phthalate biomarkers and BPA) and 1) time from ovulation to implantation; 2) type of corpus luteum rescue (timing and pattern of rise in progesterone: early, late, or no rise); and 3) rate of initial rise in hCG. RESULTS: Mono(3-carboxypropyl) phthalate (MCPP) and mono-isobutyl phthalate (MiBP) were associated with earlier implantation (6-8 days vs. 9 days (the most commonly observed); per natural log-unit, OR (95% CI) = 2.8 (1.2, 6.7) and OR (CI) = 2.1 (1.2, 3.7), respectively). Monoethyl phthalate (MEP) was associated with later implantation (10-12 days vs. 9 days); OR (CI) = 1.5 (1.0, 2.1). Compared with implantation on day 9, BPA was significantly associated with both earlier and later implantation (OR=2.2 for both). Women with concentrations above the median of monobenzyl phthalate (MBzP) (p = 0.04) or above the median of the molar sum of four di(2-ethylhexyl) phthalate metabolites (∑DEHP) (p = 0.08) had a slower initial rise in hCG. Increasing MCPP was associated with an increased odds of a late rise rescue (OR (CI) = 2.9 (1.0, 8.5); late rise vs. early rise), while increasing MEP was associated with a no rise rescue (OR (CI) = 1.6 (0.9, 2.8); no rise vs. early rise). CONCLUSIONS: The reported associations varied in their direction of effect, some potentially protective, others adverse. This may reflect the complexity with which these potential endocrine disrupting chemicals can be acting, but chance findings are also possible. Given that women continue to be exposed to these compounds (or their precursors), continued research on the effects they may have on pregnancy is warranted.

Differences in Women's Use of Medical Help for Becoming Pregnant by the Level of Urbanization of County of Residence in Georgia.

PURPOSE: Our goal was to determine if there are differences by place of residence in visiting a doctor for help getting pregnant in a population-based study. METHODS: Using data from the Furthering Understanding of Cancer, Health, and Survivorship in Adult (FUCHSIA) Women's Study, a cohort study of fertility outcomes in reproductive-aged women in Georgia, we fit models to estimate the association between geographic type of residence and seeking help for becoming pregnant. FINDINGS: The prevalence of visiting a doctor for help getting pregnant ranged from 13% to 17% across geographic groups. Women living in suburban counties were most likely to seek medical care for help getting pregnant compared with women living in urbanized counties (adjusted prevalence ratio (aPR) = 1.14, 95% CI: 0.74-1.75); among women who reported infertility this difference was more pronounced (aPR = 1.59, 95% CI: 1.00-2.53). Women living in rural counties were equally likely to seek fertility care compared with women in urbanized counties in the full sample and among women who experienced infertility. CONCLUSIONS: Women living in urban and rural counties were least likely to seek infertility care, suggesting that factors including but not limited to physical proximity to providers are influencing utilization of this type of care. Increased communication about reproductive goals and infertility care available to meet these goals by providers who women see for regular care may help address these barriers.

Which female cancer patients fail to receive fertility counseling before treatment in the state of Georgia?

OBJECTIVE: To assess which characteristics are associated with failure to receive fertility counseling among a cohort of young women diagnosed with cancer. DESIGN: Population-based cohort study. SETTING: Not applicable. PATIENT(S): A total of 1,282 cancer survivors, of whom 1,116 met the inclusion criteria for the analysis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The main outcome in this study was whether or not women reported receiving any information at the time of their cancer diagnosis on how cancer treatment might affect their ability to become pregnant. RESULT(S): Forty percent of cancer survivors reported that they did not receive fertility counseling at the time of cancer diagnosis. Women were more likely to fail to receive counseling if they had only a high school education or less or if they had given birth. Cancer-related variables that were associated with a lack of counseling included not receiving chemotherapy as part of treatment and diagnosis with certain cancer types. CONCLUSION(S): Counseling about the risk of infertility and available fertility preservation options is important to cancer patients. Additionally, counseling can make women aware of other adverse reproductive outcomes, such as early menopause and its associated symptoms. Less-educated women and parous women are at particular risk of not getting fertility-related information. Programs that focus on training not just the oncologist, but also other health care providers involved with cancer care, to provide fertility counseling may help to expand access.

Hypothyroidism after cancer and the ability to meet reproductive goals among a cohort of young adult female cancer survivors.

OBJECTIVE: To determine whether developing hypothyroidism after cancer treatment is associated with a decreased probability of women being able to meet their reproductive goals. DESIGN: A population-based cohort study. SETTING: Not applicable. PATIENT(S): A total of 1,282 cancer survivors, of whom 904 met the inclusion criteria for the analysis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Three outcomes that may indicate reduced fertility, which include failure to achieve desired family size, childlessness, and not achieving pregnancy after at least 6 months of regular unprotected intercourse. RESULT(S): We used data from the Furthering Understanding of Cancer Health and Survivorship in Adult (FUCHSIA) Women's Study to examine the association between being diagnosed with hypothyroidism after cancer and meeting reproductive goals. After adjusting for age and other potential confounders, women reporting hypothyroidism after cancer treatment were twice as likely to fail to achieve their desired family size (adjusted odds ratio [aOR] 1.91; 95% confidence interval [CI], 1.09, 3.33) and be childless (aOR 2.13; 95% CI, 1.25, 3.65). They were also more likely to report having unprotected intercourse for at least 6 months without conceiving (aOR 1.37; 95% CI, 0.66, 2.83). CONCLUSION(S): Although cancer treatments themselves are gonadotoxic, it is important to consider other medical conditions such as hypothyroidism that occur after cancer treatment when counseling patients on the risks for impaired fertility or a shortened reproductive window.

Racial Disparities in Seeking Care for Help Getting Pregnant.

BACKGROUND: Fertility counselling and treatment can help women achieve their desired family size; however, disparities exist in the utilisation of this care. METHODS: This study examines the persistence of a racial disparity in visiting a doctor for help getting pregnant by estimating the direct effect of this association using data from the Furthering Understanding of Cancer Health and Survivorship in Adult Women's Study, a population-based cohort study. This cohort included 1073 reproductive age women (22-45 years) with 28% reporting infertility. We fit log binomial models to quantify the magnitude of the racial difference in reported care seeking after adjustment for hypothesised mediators using inverse probability weighting. RESULTS: Compared with white women, black women were less likely to visit a doctor in the total population [adjusted risk ratio (RR) 0.57, 95% confidence interval (CI) 0.41, 0.80] and in the subgroup of women with infertility [RR 0.75, 95% CI 0.56, 0.99]. In addition, black women waited twice as long, on average, before seeking help compared with white women. CONCLUSIONS: There were notable racial differences in visiting a doctor for help getting pregnant in this study although reports of infertility were similar by race. These differences may be mitigated through improved communication about the range of counselling and treatment options available.

Piloting a computer assisted telephone interview: the FUCHSIA Women's Study.

BACKGROUND: Loss of fertility has been reported as an important concern of reproductive age women diagnosed with cancer. The Furthering Understanding of Cancer, Health, and Survivorship In Adult (FUCHSIA) Women's Study examines how cancer treatment affects the fertility of cancer survivors who were diagnosed during their reproductive years. In this paper we discuss the process of developing and pilot testing the FUCHSIA computer assisted telephone interview (CATI). METHODS: The CATI was developed in several phases and pilot tested twice to evaluate several aspects of the instrument including question sequencing, understandability of the questions, and women's comfort with certain questions. Participants were recruited from cancer and infertility support groups and study team contacts. RESULTS: Fifty-two women were recruited and participated in the first pilot. The participants had a mean age of 31.5 years, 17.3% had cancer, and 38.5% experienced a period of infertility. Twenty-four women participated in the second pilot with similar representation. CONCLUSIONS: The collection of detailed information on reproductive outcomes with the CATI may improve the understanding of how cancer treatment during the reproductive years affects female fertility. The pilot studies provided important information to improve the CATI before the full study. Our comprehensive recruitment strategy allowed us to interview a diverse group of women to ensure that questions and answer choices were easily interpreted, check complicated skip patterns and the flow of questions, and evaluate the length of the interview. This experience can be used to help inform others in what steps can be useful for developing telephone interviews for research studies.