Project Summary Improvements in medical care have transitioned sickle cell disease (SCD) from a disease of childhood into a long-term chronic illness. As people who have SCD become adults, parenthood becomes an important life goal for many, but little is known about their reproductive potential. Hydroxyurea, a common treatment for SCD, has been associated with decreased sperm count, but parallel studies of ovarian reserve in adult women do not exist. Ovarian reserve decreases naturally as women approach menopause, but gonadotoxic treatments may accelerate the onset of menopause resulting in a shortened period in which to have children as well as earlier onset of menopause sequelae such as sexual dysfunction, cardiovascular disease, and low bone density. Blood transfusion is also an important therapy for SCD, but repeated transfusions (chronic or episodic) result in iron overload, the accumulation of iron in some organs and tissues. In women with transfusion-dependent β- thalassemia, this has been associated with decreased ovarian reserve, which may reflect iron accumulation in the ovary. Further, iron toxicity to the anterior pituitary may impair production of gonadal hormones. A study of iron overload in adolescents with SCD and studies of women with transfusion-dependent β-thalassemia appear to support this possibility. Further, in women with transfusion-dependent β-thalassemia, the prevalence of hypogonadotropic hypogonadism and amenorrhea are high. Thus, there are plausible mechanisms by which SCD treatments and complications may shorten the reproductive window of women with SCD and affect their fertility, but there are almost no studies of reproductive health in this vulnerable population. We will address this gap through the following aims: 1) We will determine whether women with SCD have lower ovarian reserve than women without SCD and 2) We will determine whether women with SCD are at increased risk of infertility compared with women without SCD. We will evaluate these aims by iron overload status and by treatment with hydroxyurea. We are uniquely positioned to complete the proposed work because we will recruit women from the Grady Hospital Comprehensive SCD Clinic, which serves the largest SCD patient population in the country. Further, we will build on our extensive prior experience studying reproductive health in cancer survivors and in women with lupus. Women with SCD, predominately African American women living in metropolitan Atlanta, will be compared with a population-based sample of African American women living in metropolitan Atlanta that we recruited previously. We will assess ovarian reserve based on serum anti-Müllerian hormone. Infertility will be defined several ways including as not getting pregnant after 12 months of regular, unprotected intercourse. Our previously developed, in-depth interview will provide information on infertility and potential confounders. We will abstract hydroxyurea, iron overload, and SCD care info...