Introduction Female cancer survivors who received gonadotoxic cancer treatment are at risk for profound diminished ovarian reserve and/or primary ovarian insufficiency with resulting infertility, which can be associated with distress and decreased quality of life.. Despite prioritizing future parenthood, many survivors are unsure of the impact of their treatment on their future fertility, and little is known about the perceived reproductive health needs and factors associated with receipt of a fertility status assessment (FSA). There is a lack of developmentally appropriate reproductive health decisional support interventions available for emerging adult cancer survivors. This study will explore the perceived reproductive health needs of emerging adult female survivors of childhood cancer and to identify decisional and contextual factors that influence pursuit of FSA using an explanatory sequential quantitative to qualitative mixed methods design. Methods and analysis This study will enroll 325 female survivors (aged 18 to 29 years and >1-year post treatment; diagnosed with cancer < age 21 years) from four cancer centers in the United States. Sociodemographic and developmental factors, reproductive knowledge and values, decisional needs, and receipt of an FSA will be assessed through a web-based survey. Informed by survey findings, a subset of participants will be recruited for qualitative interviews to explore decisional factors associated with uptake of an FSA. Clinical data will be abstracted from the medical records. Multivariable logistic regression models will be developed to identify factors associated with FSA and qualitative descriptive analysis will be used to develop themes from the interviews. Quantitative and qualitative findings will be merged using a joint display to develop integrated study conclusions and direct future interventional research.

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.

Objective To determine whether tamoxifen use is associated with decreased ovarian reserve and decreased likelihood of having a child after a breast cancer diagnosis, using data from the Furthering Understanding of Cancer, Health, and Survivorship in Adult (FUCHSIA) Women Study. Design Population-based cohort study. Setting Not applicable. Patient(s) Three hundred ninety-seven female breast cancer survivors aged 22–45 years whose cancer was diagnosed between ages 20 and 35 years and who were at least 2 years after diagnosis; 108 survivors also participated in a clinic visit. Intervention(s) None. Main Outcome Measure(s) Time to first child after cancer diagnosis, clinical measures of ovarian reserve (antimüllerian hormone [AMH] and antral follicle count [AFC] ) after cancer. Result(s) Women who had ever used tamoxifen were substantially less likely to have a child after the breast cancer diagnosis (hazard ratio [HR] 0.29; 95% confidence interval [CI] , 0.16, 0.54) than women who had never used tamoxifen. After adjusting for age at diagnosis, exposure to an alkylating agent, and race, the HR was 0.25 (95% CI, 0.14, 0.47). However, after adjusting for potential confounders, women who had used tamoxifen had an estimated geometric mean AMH level 2.47 times higher (95% CI, 1.08, 5.65) than women who had never taken tamoxifen. Antral follicle count was also higher in the tamoxifen group compared with the tamoxifen nonusers when adjusted for the same variables (risk ratio 1.21; 95% CI, 0.84, 1.73). Conclusion(s) Breast cancer survivors who had used tamoxifen were less likely to have a child after breast cancer diagnosis compared with survivors who never used tamoxifen. However, tamoxifen users did not have decreased ovarian reserve compared with the tamoxifen nonusers.

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.

Background: Previous studies have reported that hyperthyroid and hypothyroid women experience menstrual irregularities more often compared with euthyroid women, but reasons for this are not well-understood and studies on thyroid hormones among euthyroid women are lacking. In a prospective cohort study of euthyroid women, this study characterised the relationship between thyroid hormone concentrations and prospectively collected menstrual function outcomes. Methods: Between 2004-2014, 86 euthyroid premenopausal women not lactating or taking hormonal medications participated in a study measuring menstrual function. Serum thyroid hormones were measured before the menstrual function study began. Women then collected first morning urine voids and completed daily bleeding diaries every day for three cycles. Urinary oestrogen and progesterone metabolites (estrone 3-glucuronide (E13G) and pregnanediol 3-glucuronide (Pd3G)) and follicle-stimulating hormone were measured and adjusted for creatinine (Cr). Results: Total thyroxine (T4) concentrations were positively associated with Pd3G and E13G. Women with higher (vs lower) T4 had greater luteal phase maximum Pd3G (Pd3G = 11.7 μg/mg Cr for women with high T4 vs Pd3G = 9.5 and 8.1 μg/mg Cr for women with medium and low T4, respectively) and greater follicular phase maximum E13G (E13G = 41.7 ng/mg Cr for women with high T4 vs E13G = 34.3 and 33.7 ng/mg Cr for women with medium and low T4, respectively). Conclusions: Circulating thyroid hormone concentrations were associated with subtle differences in menstrual cycle function outcomes, particularly sex steroid hormone levels in healthy women. Results contribute to the understanding of the relationship between thyroid function and the menstrual cycle, and may have implications for fertility and chronic disease.

Background: Brominated flame retardants, including polybrominated biphenyls (PBB), are persistent compounds reported to affect sex hormones in animals; less is known about potential effects in humans. An industrial accident in 1973–1974 exposed Michigan residents to PBB through contaminated food. We examined whether this exposure to PBB had long-term effects on menstrual cycle function. Methods: In 2004–06, we recruited reproductive-aged women in the Michigan PBB Registry who were not pregnant, lactating, or taking hormonal medications. Participants kept daily diaries and provided daily urine for up to 6 months. We assayed urine samples for estrone 3-glucuronide (E13G), pregnanediol 3-glucuronide (Pd3G), and follicle stimulating hormone (FSH). We fit linear mixed models among women aged 35–42 years to describe the relation between serum PBB levels and log-transformed, creatinine-adjusted daily endocrine levels among women who were premenarchal during the exposure incident in 1973–74 (n=70). Results: We observed that high (>3.0 parts per billion (ppb)) and medium (>1.0–3.0 ppb) PBB exposure were associated with lower E13G levels across the menstrual cycle and lower FSH levels during the follicular phase, compared with low PBB exposure (≤1.0 ppb). High PBB exposure was also associated with lower Pd3G levels across the cycle compared with low PBB exposure, whereas Pd3G levels were similar in women with medium and low PBB exposure. Conclusions: Our results are consistent with a hypothesized effect of exposure to an exogenous estrogen agonist but the modest sample size of the study requires cautious interpretation.

Primary or premature ovarian insufficiency (POI) is the most common long-term complication experienced by girls and women with classic galactosemia; more than 80% and perhaps more than 90% are affected despite neonatal diagnosis and careful lifelong dietary restriction of galactose. In this review we explore the complexities of timing and detection of galactosemia-associated POI and discuss potential underlying mechanisms. Finally, we offer recommendations for follow-up care with current options for intervention.

Classical galactosemia (CG) is an inborn error of galactose metabolism. Evidence-based guidelines for the treatment and follow-up of CG are currently lacking, and treatment and follow-up have been demonstrated to vary worldwide. To provide patients around the world the same state-of-the-art in care, members of The Galactosemia Network (GalNet) developed an evidence-based and internationally applicable guideline for the diagnosis, treatment, and follow-up of CG. The guideline was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. A systematic review of the literature was performed, after key questions were formulated during an initial GalNet meeting. The first author and one of the working group experts conducted data-extraction. All experts were involved in data-extraction. Quality of the body of evidence was evaluated and recommendations were formulated. Whenever possible recommendations were evidence-based, if not they were based on expert opinion. Consensus was reached by multiple conference calls, consensus rounds via e-mail and a final consensus meeting. Recommendations addressing diagnosis, dietary treatment, biochemical monitoring, and follow-up of clinical complications were formulated. For all recommendations but one, full consensus was reached. A 93 % consensus was reached on the recommendation addressing age at start of bone density screening. During the development of this guideline, gaps of knowledge were identified in most fields of interest, foremost in the fields of treatment and follow-up.

Background: Michigan residents were directly exposed to endocrine-disrupting compounds, polybrominated biphenyl (PBB) and polychlorinated biphenyl (PCB). A growing body of evidence suggests that exposure to certain endocrine-disrupting compounds may affect thyroid function, especially in people exposed as children, but there are conflicting observations. In this study, we extend previous work by examining age of exposure's effect on the relationship between PBB exposure and thyroid function in a large group of individuals exposed to PBB. Methods: Linear regression models were used to test the association between serum measures of thyroid function (total thyroxine (T4), total triiodothyronine (T3), free T4, free T3, thyroid stimulating hormone (TSH), and free T3: free T4 ratio) and serum PBB and PCB levels in a cross-sectional analysis of 715 participants in the Michigan PBB Registry. Results: Higher PBB levels were associated with many thyroid hormones measures, including higher free T3 (p = 0.002), lower free T4 (p = 0.01), and higher free T3: free T4 ratio (p = 0.0001). Higher PCB levels were associated with higher free T4 (p = 0.0002), and higher free T3: free T4 ratio (p = 0.002). Importantly, the association between PBB and thyroid hormones was dependent on age at exposure. Among people exposed before age 16 (N = 446), higher PBB exposure was associated with higher total T3 (p = 0.01) and free T3 (p = 0.0003), lower free T4 (p = 0.04), and higher free T3: free T4 ratio (p = 0.0001). No significant associations were found among participants who were exposed after age 16. No significant associations were found between TSH and PBB or PCB in any of the analyses conducted. Conclusions: This suggests that both PBB and PCB are associated with thyroid function, particularly among those who were exposed as children or prenatally.

Purpose: To evaluate the difference in tubal ligation use between rural and urban counties in the state of Georgia, USA. Methods: The study population included 2,160 women aged 22-45. All participants completed a detailed interview on their reproductive histories. County of residence was categorized using the National Center for Health Statistics Urban-Rural Classification Scheme. We estimated the association between urbanization of county of residence and tubal ligation using Cox regression. Among women with a tubal ligation, we examined factors associated with prior contraception use and the desire for more children. Findings: After adjustment for covariates, women residing in rural counties had twice the incidence rate of tubal ligation compared with women in large metropolitan counties (adjusted hazard ratio [aHR] = 2.0, 95% CI = 1.4-2.9) and were on average 3 years younger at the time of the procedure. No differences were observed between small metropolitan and large metropolitan counties (aHR = 1.1, CI = 0.9-1.5). Our data suggest that women from large metropolitan counties are slightly more likely than women from rural counties to use hormonal contraception or long-acting reversible contraception prior to tubal ligation and to desire more children after tubal ligation. Conclusions: Women from rural counties are more likely to undergo a tubal ligation than their urban counterparts. Our results suggest that circumstances regarding opting for tubal ligation may differ between urban and rural areas, and recommendations of alternative contraceptive options may need to be tailored differently for rural areas.