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Objective: To determine whether European Americans with polycystic ovary syndrome (PCOS) exhibit genetic differences associated with PCOS status and phenotypic features.Design: Case-control association study in European Americans.Setting: Academic center.Subject(s): Women with PCOS diagnosed with the use of the National Institutes of Health criteria (n = 532) and control women with regular menstrual cycles and no evidence of hyperandrogenism (n = 432).Intervention(s): Blood was drawn for measurement of sex steroids, metabolic parameters, and genotyping.Main Outcome Measure(s): Associations among PCOS status, phenotype, and genetic background identified with the use of principal component analysis.Result(s): Principal component analysis identified five principal components (PCs). PC1 captured northwest-to-southeast European genetic variation and was associated with PCOS status. Acanthosis was associated with southern European ancestry, and larger waist:hip ratio was associated with northern European ancestry. PC2 was associated with east-to-west European genetic variation and cholesterol levels.Conclusion(s): These data provide evidence for genetic influence based on European ethnicity in women with PCOS. There is also evidence for a genetic component in the phenotypic features of PCOS within a mixed European population. The data point to the need to control for population stratification in genetic studies in women of mixed European ethnicity. They also emphasize the need for better studies of PCOS prevalence and phenotype as a function of genetic background. [ABSTRACT FROM AUTHOR]

Objective: To determine age-based criteria for polycystic ovary morphology.Design: Cross-sectional, case-control design.Setting: Outpatient setting.Subject(s): Women with polycystic ovary syndrome (PCOS) defined by hyperandrogenism and irregular menses (n = 544) and controls with regular menses and no evidence of hyperandrogenism (n = 666) participated. Parameters were tested in a second cohort of women with PCOS (n = 105) and controls (n = 32) meeting the same criteria.Intervention(s): Subjects underwent a pelvic ultrasound documenting ovarian volume and maximum follicle number in a single plane.Main Outcome Measure(s): A receiver operating characteristic curve was constructed to determine the ovarian volume and follicle number with the best sensitivity and specificity to define PCOS for age groups at approximately 5-year intervals from age 18 to >44 years.Result(s): The best sensitivity and specificity were obtained using a threshold volume of 12 mL and 13 follicles for ages ≤24 years, 10 mL and 14 follicles for ages 25-29 years, 9 mL and 10 follicles for ages 30-34 years, 8 mL and 10 follicles for ages 35-39 years, 10 mL and 9 follicles for ages 40-44 years, and 6 mL and 7 follicles for ages >44 years. Data from a second cohort confirmed the need to decrease volume and follicle number with increasing age to diagnose PCOS. Polycystic ovary morphology was most accurate at predicting the PCOS diagnosis for women ages 30-39 years.Conclusion(s): The ovarian volume and follicle number threshold to define polycystic ovary morphology should be lowered starting at age 30. [ABSTRACT FROM AUTHOR]

Objective: To update clinicians on the reproductive implications of premutations in FMR1 (fragile X mental retardation 1). Fragile X syndrome, a cause of mental retardation and autism, is due to a full mutation (>200 CGG repeats). Initially, individuals who carried the premutation (defined as more than 55 but less than 200 CGG repeats) were not considered at risk for any clinical disorders. It is now recognized that this was incorrect, specifically with respect to female reproduction. Design and Setting: Literature review and consensus building at two multidisciplinary scientific workshops. Conclusion(s): Convincing evidence now relates the FMR1 premutation to altered ovarian function and loss of fertility. An FMR1 mRNA gain-of-function toxicity may underlie this altered ovarian function. There are major gaps in knowledge regarding the natural history of the altered ovarian function in women who carry the FMR1 premutation, making counseling about reproductive plans a challenge. Women with premature ovarian failure are at increased risk of having an FMR1 premutation and should be informed of the availability of fragile X testing. Specialists in reproductive medicine can provide a supportive environment in which to explain the implications of FMR1 premutation testing, facilitate access to testing, and make appropriate referral to genetic counselors. [Copyright &y& Elsevier]