Fertility and female reproductive rights have become hot-button issues in recent years. While the problem of infertility has been around since antiquity, we now possess new ways of treating infertility that were previously unthinkable, such as in vitro fertilization, freezing of the eggs and sperm, and surrogacy. The new spectrum of therapeutic options to treat infertility has raised legal and ethical concerns for some. 

Even in the age of modern medicine, infertility remains a stubbornly persistent problem. Studies estimate that around 12% of females receive infertility services. In the Journal of the American Medical Association, Carson and Kallen wrote, “The most common causes of infertility are ovulatory dysfunction, male factor infertility, and tubal disease. The remaining 15% of infertile couples have ‘unexplained infertility.’” 

Studies have also demonstrated that lifestyle factors can increase the odds of infertility. For example, cigarette smoking and obesity have both been associated with higher rates of infertility. Needless to say, female fecundity also ceases when menopause begins. 

Patients with certain chronic diseases such as sickle cell disease (SCD) are a group of individuals for whom the risk of infertility has always been an underlying cause for concern. SCD is a significant risk factor for infertility, and since SCD tends to be diagnosed at a very young age, many patients live their whole lives unsure of their fertility status until they choose to conceive. 

A Predisposition to Infertility 

Notwithstanding the enormous disease burden of SCD in terms of the risk of painful, disruptive vaso-occlusive crises, patients with SCD also have to contend with the substantive probability that they may be infertile. 

How does SCD predispose one to infertility? There are several hypotheses. In the Journal of Clinical Medicine, Nickel and colleagues wrote, “SCD pathophysiologies, inflammation and hypoxic-ischemic injury, likely damage the ovaries.”

Studies suggest that in female patients with SCD, there is a decrease in vascularity in the outer layer of the ovarian cortex; this decrease in blood supply may then accelerate follicular atresia. This is in line with findings that suggest that women with SCD experience an accelerated decline in their ovarian reserve. 

Read more about SCD etiology

Another potential cause for infertility in patients with SCD lies in the type of treatment used in SCD, namely hydroxyurea. Hydroxyurea is an indispensable medication in SCD and is used to reduce the frequency of vaso-occlusive crises and acute chest syndrome episodes. 

There are two things we know about hydroxyurea. First, studies have shown that women with SCD who were on hydroxyurea had a diminished ovarian reserve. Second, patients on hydroxyurea are at a higher risk of teratogenicity when pregnant. Studies have shown pregnant women with SCD to be at a higher risk of having offspring with birth defects, including neuronal deformities and deformities in the extremities.

Not an All-Female Issue

The risk of infertility by virtue of being on hydroxyurea treatment affects men too. Studies on murine models have demonstrated sperm abnormalities upon hydroxyurea treatment. “From then, several papers have been done on the effect of hydroxyurea on fertility in sickle cell patients, which have demonstrated that hydroxyurea is linked to oligospermia and other sperm abnormalities,” Huang and Muneyyirci-Delale wrote in Andrology. 

They highlighted the fact that one of the main causes of infertility in men occurs before reproductive age, at the onset of puberty. Studies have demonstrated that young male patients with SCD experience a decrease in bone age, height, and weight during puberty compared to healthy individuals. 

Read more about SCD patient education 

In addition, the damage to growth also depends on how well the SCD is managed. Studies have found that children receiving blood transfusions every 3 to 5 weeks have normal average weight and height, while children who did not receive blood transfusions experienced a decrease in growth parameters. 

However, blood transfusions can also be a source of damage, particularly when iron overload occurs. Iron overload is always a cause for concern in patients who need to receive frequent blood transfusions, and untreated iron overload can lead to endocrinopathy and other health issues in growing boys. 

Treating Infertility 

In light of the increased risk of infertility in both male and female patients with SCD, these patients should be prime candidates for infertility treatments. The standard protocol for managing infertility remains identifying the source of the infertility—meaning whether the issue lies with the male or female in a relationship, or both. Just because the risk of infertility is higher in SCD does not preclude infertility from being caused by other factors, such as the ones listed in the introduction of this article. 

In addition to providing fertility services to help couples in which one or both parties have SCD, it is also important that sound prenatal counseling be offered to women with SCD who are pregnant. In addition to genetic counseling, they should also be offered a frank assessment of the risks of teratogenicity. The goal is to ensure that couples who manage to get pregnant are well educated on the risks associated with a pregnancy in a patient with SCD. 

Ultimately, patients with SCD have reasons to hope. First, as medical researchers inch closer to a potential cure for SCD, there is a possibility that they may be able to live lives free of this disease. In addition, developments in fertility medicine mean that patients with SCD have more options to have a safe and viable pregnancy if desired. 


Ghafuri DL, Stimpson SJ, Day ME, James A, DeBaun MR, Sharma D. Fertility challenges for women with sickle cell diseaseExpert Rev Hematol. 2017;10(10):891-901. doi:10.1080/17474086.2017.1367279

Nickel RS, Maher JY, Hsieh MH, Davis MF, Hsieh MM, Pecker LH. Fertility after curative therapy for sickle cell disease: a comprehensive review to guide careJ Clin Med. 2022;11(9):2318. doi:10.3390/jcm11092318

Carson SA, Kallen AN. Diagnosis and management of infertility: a reviewJAMA. 2021;326(1):65-76. doi:10.1001/jama.2021.4788

Huang AW, Muneyyirci-Delale O. Reproductive endocrine issues in men with sickle cell anemiaAndrology. 2017;5(4):679-690. doi:10.1111/andr.12370