Patients with sickle cell disease (SCD) face a complex array of challenges that can affect fertility and other aspects of reproductive health. In a paper published in March 2023 in The Lancet Haematology, Lydia H. Pecker, MD, director of the Young Adult Clinic at the Johns Hopkins Sickle Cell Center for Adults in Baltimore, and colleaguesproposedthat integrating standardized fertility care into SCD treatment is a requisite of high-quality, personalized care for this patient population.1

One common fertility-related issue in SCD is reduced sperm count due to hydroxyurea treatment. In a study of 35 men with SCD, for example, researchers observed a hydroxyurea-induced decrease in sperm count from 61.6 million to 0.63 million.2 In some cases, sperm counts may improve during temporary cessation of hydroxyurea, according to Alexis A. Thompson, MD, MPH, chief of the division of hematology at the Children’s Hospital of Philadelphia.

“For women, SCD is associated with increased risk of miscarriages, premature delivery, and maternal death,” Dr Thompson explained.3 “Pregnancy-related anemia is much worse in SCD and can be associated with other sickle cell complications like acute chest syndrome.” She also pointed to data from Dr Pecker and other researchers showing diminished ovarian reserve in women with SCD.,4,5

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Despite these myriad issues, fertility care is often not prioritized in SCD management. “Hematologists do not routinely assess fertility in practice, but there is an opportunity to ensure that screening is included as part of comprehensive care,” Dr Thompson stated. “Proper evaluation and management of premature ovarian insufficiency ideally should be performed in consultation with fertility specialists, but certainly having discussions with our patients during routine visits may allow more of them to receive timely reproductive assessments and care.”

In an in-depth discussion with Hematology Advisor, Dr Pecker further described the scope of fertility challenges in SCD as well as measures needed to address these as an integral part of SCD care. 

What are examples of issues that can affect fertility in individuals with SCD?

Dr Pecker:
SCD may be understood as a fertility risk in as much as the disease causes pain, hospitalizations, and social isolation and is associated with lower health-related quality of life. Also, all people with SCD will pass a hemoglobinopathy trait to their offspring, and so some people are at risk for having a child with SCD, depending on trait status of the other parent. A teaching tool we developed and published about that is now freely available on the Sickle Cell Reproductive Health Education Directive website.6

For people with testicles, fertility concerns include low testosterone, priapism, erectile dysfunction, and abnormal sperm morphology and counts. Hydroxyurea is toxic to sperm, and this effect seems to be reversible.7

For people with ovaries, dyspareunia occurs, ovarian reserve declines faster than the general population, and — associated with the decline in egg supply — menopause onset may be earlier.8 Hydroxyurea treatment is associated with lower egg supply, but whether this is an effect of the drug or a proxy marker for more severe SCD is not worked out. Pregnancy is also high risk.