In the United States, patients with sickle cell anemia (SCA) now survive into adulthood, making reproductive concerns increasingly important for this population. Little is known about how SCA affects women?s reproductive capacity. The ovaries may be among the end-organs injured by the oxidative and hypoxic- ischemic injury of SCA. Hydroxyurea, a chemotherapeutic used to treat SCA starting as early as 9 months of age, may also affect fertility. Methodologically rigorous studies have not yet been performed to identify whether women with SCA have compromised fertility as a consequence of baseline SCA or as a consequence of treatments for SCA. This knowledge is especially important because fertility concerns are a barrier to SCA treatment, and because fertility evaluation and preservation strategies exist, but indications for their use in women with SCA are absent. This study proposes measuring anti-mullerian hormone, an established biomarker of ovarian reserve, in samples from the Multi-Center Study of Hydroxyurea, the randomized placebo-controlled trial of hydroxyurea in adults with SCA. Anti-mullerian hormone levels will be compared in hydroxyurea and placebo treated subjects and within the placebo-treated group, the association of clinical characteristics with anti-mullerian hormone levels will be analyzed. Samples from this well phenotyped cohort provide an opportunity to study how untreated SCA and hydroxyurea may affect a marker of ovarian reserve in women with SCA. Another placebo-controlled trial of hydroxyurea in adults with SCA will never be performed. Thus, this research will serve as a springboard for prospective research on fertility markers in females with SCA. 1

Public Health Relevance

A paucity of research informs our knowledge of how baseline sickle cell anemia or its treatments affects fertility in women with sickle cell anemia, and this lack of knowledge contributes to barriers to physician prescribing and patient acceptance of evidence-based treatments. Research is needed to determine whether baseline sickle cell anemia or therapies for sickle cell anemia compromise ovarian reserve and future fertility in affected patients. We propose to measure anti-mullerian hormone, a marker of ovarian reserve, in the well phenotyped female participants of the Multi-Centered Study of Hydroxyurea, the randomized placebo-controlled study of hydroxyurea in adults with sickle cell anemia.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HL144973-02
Application #
9788509
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Ochocinska, Margaret J
Project Start
2018-09-15
Project End
2020-08-31
Budget Start
2019-09-01
Budget End
2020-08-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205