Table 2. Qualitative synthesis of studies included in the systematic review.
Author/year(country) Objective Method AMH Main results
Study design Population Sample Reference value Normal Reduced Very low
Elchuriet al.,2015 (USA) To describe AMH and FSH levels in female SCD treated with supportive care (SC), hydroxyurea (HU) and transplantation (HSCT). Cross-sectional Women (HbSS or Hb Sβ Thalassemia) Age between 10-21 years old N=76 Grouped according to SCD therapy: -supportive care (14)-receiving HU (33)-performing HSCT(09) Normal:≥5°percentile*. Reduced:<5°percentile. Very low: <5°percentile and FSH >40IU/L SC=100% HU=75.8% HSCT=0.0% SC=0.0% HU=24.2% HSCT=11.1% SC=0.0% HU=0.0% HSCT=88.9% The adult patient treated with HU had reduced ovarian reserve while the adult patient undergoing HSCT had premature ovarian failure, with FSH levels at menopause.
Kopeikaet al.,2019 (United Kingdom) Assess how ovarian reserve and/or iron overload in SCD women could contribute to gonadal dysfunction/ovarian reserve ControlCase Women (all genotypes) Age between 25-45 years old N=123 50 cases 73 controls Matching: (age, ethnicity, regular cycles, AMH measurement) Negligible: <1.5 pmol/lreduced: 1.5 to 6.5 pmol/lnormal 6.6 to 19.8 pmol/l; high:>19.8 pmol/l) SC=45% Cont.=60% SC=28% Cont.=25% SC=27% Cont.=15% SCD patients of reproductive age had significantly lower levels of AMH (7.6 vs. 13.4pmol/l, p=0.01), which may be indicative of reduced ovarian reserve. SCD patients were significantly more likely to have lower AMH compared to the control group (OR 2.6 (CI 1.1-6.5, p=0.02), adjusted for HU (16% use HU). HAM also showed no correlation with HU treatment and age.
Peckeret al.,2020 (Multicenter) To test the hypotheses that (1) women participating in the Multicenter Study of Hydroxyurea (MSH) would have lower AMH levels than ageand sex-matched reference values and (2) that HU exposure is associated with lower levels from AMH Cross-sectional Women (HBSS) adults N=93 HU = 86 CS=07 Normal ≥1ng/ml Decreased ovarian reserve <1ng/ml --- --- --- AMH is normal in young women without exposure to HU, although lower than reference values for women of the same age. There is a trend towards higher AMH levels in subjects randomized to placebo compared to HU; this difference was significant at ages 30 to 35 years (mean AMH 1.23 vs. 0.87 ng/ml, p<0.001) and 40 to 46 years (median AMH 0.045 vs. 0.05 ng/ml, p=0<005). HbSS genotype and HU therapy are risk factors for premature ovarian aging and reduced reproductive life expectancy
Garbaet al.,2021 (Nigeria) To determine and compare the ovarian reserve of Nigerian women with and without SCD treated at a University Hospital Cross-sectional Women (HbSS) Age between 18-45 years and regular menses at the time of the study. N=166 83 cases (Pairing: age) Controls: 83 (HbAA) Low (0.15 - 1.14ng/ml) Normal (1.15-2.56ng/ml) High (>2.65ng/ml) SC=16.9% (High: 61.4%) Cont.=6.0% (High: 83.1%) SC= 21.7% Cont.= 0.8% Mean AMH was significantly lower in women with HbSS (3.64 ± 0.65 ng/ml vs 7.35±1.19 ng/ml, p<0.001). After controlling for possible confounding variables (such as age and BMI), the serum AMH level was about 4.42 ng/mL lower among HbSS participants compared to HbAA participants (adjusted β = -4.42, 95% CI: -5.88 to -2.96, p value <0.001). Women with HbSS demonstrated decreased ovarian reserve when compared with age-matched women with HbAA.

*SC = Women receiving supportive care only - no use of HU and HSCT
*The b5th percentile AMH concentrations for age-matched controls were classified as having low AMH: 1.07 pmol/L (0.15 ng/mL) for 10-12 years, 3.14 pmol/L (0.44 ng/mL) mL) for 13-15 years, 9.21 pmol/L (1.29 ng/mL) for 16-18 years, and 5.07pmol/L (0.71 ng/mL) for 19-21 years.