The impact of sickle cell disease and its treatment on ovarian reserve in reproductive-aged Black women

Abstract

We compared serum anti-Mullerian hormone (AMH) levels in women with sickle cell disease (SCD) (n = 152) to those of Black comparison women (n = 128) between the ages of 20 and 45 years and evaluated the impact of hydroxyurea (HU) and iron overload on ovarian reserve in those with SCD. SCD treatment was abstracted from medical records. Linear regression models were fit to examine the relationship between log(AMH) and SCD, adjusting for age. The analysis was repeated to account for HU use (current, previous, never) and iron overload (ferritin ≥1000 ng/mL vs. <1000 ng/mL). AMH estimates among women with SCD were lower than those among comparison women (2.23, 95% confidence interval [CI] 1.80-2.76 vs. 4.12, 95% CI 3.11-5.45, respectively). Women with SCD who were currently using HU had 63% lower (95% CI 43-76) AMH values than comparison women; those with SCD with prior or no HU use also had lower AMH estimates than comparison women, but the difference was less pronounced. There were no differences in predicted AMH values among women with SCD for those with and without iron overload. Women with SCD and low AMH may have a shorter reproductive window and may benefit from referral to a reproductive specialist.

Keywords: blood transfusion; hydroxyurea; iron overload; ovarian reserve; sickle cell disease.

Figure 1.

Anti-Mullerian hormone (AMH) values of women with sickle cell disease (SCD)¹ and comparison women² among a cohort of reproductive-aged Black/African American women stratified by SART age category ¹AMH values for women with SCD stratified by age – 20–34 years: 2.83, IQR 1.50–3.80; 35–37 years: 1.47, IQR 0.86–2.22; 38–40 years: 0.47, IQR 0.17–0.93; >40 years: 0.42, IQR 0.14–0.66 ²AMH values for comparison women without SCD stratified by age – 20–34 years: 3.70, IQR 2.56–6.94; 35–37 years: 3.01, IQR 2.24–5.59; 38–40 years: 1.84, IQR 0.97–2.77; >40 years: 0.54, IQR 0.24–0.98

Figure 2.

Estimated anti-Mullerian hormone (AMH) values and 95% confidence interval¹ for women with sickle cell disease (SCD) stratified by hydroxyurea (HU) use (current, previous, never)² and comparison women among a cohort of reproductive-aged Black/African American women. ¹Estimates are for a 20–34-year-old woman ²SCD group restricted to HbSS and HbS–Beta⁰ genotypes ³Contraceptives that may decrease AMH values included combined oral contraceptives, progestin-only pills, hormonal implant, vaginal ring, and contraceptive injection; participants were dichotomized into users and non-users

Figure 3.

Estimated anti-Mullerian hormone (AMH) values and 95% confidence interval¹ for women with sickle cell disease (SCD) stratified by iron overload status and comparison women among a cohort of reproductive-aged Black/African American women. ¹Estimates are for a 20–34-year-old woman ²Contraceptives that may decrease AMH values included combined oral contraceptives, progestin-only pills, hormonal implant, vaginal ring, and contraceptive injection; participants were dichotomized into users and non-users

Figure 4.

Estimated anti-Mullerian hormone (AMH) values and 95% confidence interval¹ for reproductive-aged Black/African American women with sickle cell disease (SCD) stratified by iron overload status and history of ever using hydroxyurea (HU). ¹Estimates are for a 20–34-year-old woman