Characteristics (notably AMH levels) of the patients with sickle cell disease as a function of HC exposure, together with control values and age-adjusted reference values
| . | Control patients (n = 130) . | Patients with SCD (n = 65) . | P value . | Patients in the non-HC group (n = 32) . | Patients in the HC group (n = 33) . | P value . |
|---|---|---|---|---|---|---|
| Age (y), median [range] | 25.7 [20.5-40.2] | 25.0 [16.0-40.0] | .024 | 25.0 [18.0-37.0] | 24.0 [16.0-40.0] | .567 |
| BMI (kg/m2), median [range] | 23.3 [17.3-37.6] | 22.3 [17.1-39.6] | .2983 | 22.3 [17.6-33.7] | 22.0 [17.1-39.6] | .9538 |
| SCD genotypes, n (%) | ||||||
| SS | — | 51 (78) | N/A | 24 (75) | 27 (81) | .5580 |
| SC | — | 8 (12) | N/A | 7 (22) | 1 (3) | N/A |
| Sβ0 | — | 3 (5) | N/A | 0 (0) | 3 (9) | N/A |
| Sβ+ | — | 3 (5) | N/A | 1 (3) | 2 (6) | N/A |
| Disease complications, n (%) | — | |||||
| Osteonecrosis | — | 6 (9) | N/A | 1 (3) | 5 (15) | .1968 |
| Retinopathy | — | 11 (17) | N/A | 5 (16) | 6 (18) | 1.000 |
| Nephropathy | — | 7 (11) | N/A | 3 (9) | 4 (12) | N/A |
| Cerebral vasculopathy | — | 29 (45) | N/A | 15 (46) | 14 (42) | .8050 |
| Liver hemochromatosis | — | 28 (43) | N/A | 13 (40) | 15 (45) | .8036 |
| Acute chest syndrome | — | 29 (45) | N/A | 9 (28) | 20 (60) | .1778 |
| Vaso-occlusive episode (at least 1 in the last 12 months) | — | 40 (62) | N/A | 17 (53) | 23 (69) | 1.000 |
| Biochemical and hematologic features | ||||||
| Hemoglobin (g/dL) | — | 9.2 [7.2-12.2] | N/A | 9.5 [7.2-12.2] | 9.0 [7.2-11.8] | .2089 |
| LDH (UI/L), median [range] | — | 348 [27-770] | N/A | 358 [27-770] | 348 [193-531] | .2403 |
| Reticulocyte count (G/L), median [range] | — | 223 [49-674] | N/A | 225 [78-674] | 223 [49-611] | .3207 |
| MCV (fl), median [range] | — | 84 [59-122] | N/A | 82 [59-93] | 86 [65-122] | .0075 |
| HbF (%), median [range] | — | 2.3 [0.4-29.1] | N/A | 1.6 [0.4-6.0] | 3.7 [0.5-29.1] | .0008 |
| HC | ||||||
| Dose (mg/kg per day), median [range] | — | 18.99 [7.14-36.11] | N/A | — | 18.99 [7.14-36.11] | N/A |
| Duration (day), median [range] | — | 2491 [140 –7154] | N/A | — | 2491 [140 –7154] | N/A |
| Transfusion program, n (%) | — | 41 (63) | N/A | 22 (69) | 19 (58) | .8155 |
| Motherhood, n (%) | — | 30 (46) | N/A | 15 (46) | 15 (45) | 1.000 |
| AMH (ng/mL), median [range] | 3.40 [0.60-17.60] | 1.51 [0.01-9.10] | < .0001 | 2.47 [0.01-9.10] | 1.31 [0.01-5.54] | .01 |
| DOR, n (%) | 9 (7) | 19 (29) | .011 | 7 (22) | 12 (36) | .27 |
| . | Control patients (n = 130) . | Patients with SCD (n = 65) . | P value . | Patients in the non-HC group (n = 32) . | Patients in the HC group (n = 33) . | P value . |
|---|---|---|---|---|---|---|
| Age (y), median [range] | 25.7 [20.5-40.2] | 25.0 [16.0-40.0] | .024 | 25.0 [18.0-37.0] | 24.0 [16.0-40.0] | .567 |
| BMI (kg/m2), median [range] | 23.3 [17.3-37.6] | 22.3 [17.1-39.6] | .2983 | 22.3 [17.6-33.7] | 22.0 [17.1-39.6] | .9538 |
| SCD genotypes, n (%) | ||||||
| SS | — | 51 (78) | N/A | 24 (75) | 27 (81) | .5580 |
| SC | — | 8 (12) | N/A | 7 (22) | 1 (3) | N/A |
| Sβ0 | — | 3 (5) | N/A | 0 (0) | 3 (9) | N/A |
| Sβ+ | — | 3 (5) | N/A | 1 (3) | 2 (6) | N/A |
| Disease complications, n (%) | — | |||||
| Osteonecrosis | — | 6 (9) | N/A | 1 (3) | 5 (15) | .1968 |
| Retinopathy | — | 11 (17) | N/A | 5 (16) | 6 (18) | 1.000 |
| Nephropathy | — | 7 (11) | N/A | 3 (9) | 4 (12) | N/A |
| Cerebral vasculopathy | — | 29 (45) | N/A | 15 (46) | 14 (42) | .8050 |
| Liver hemochromatosis | — | 28 (43) | N/A | 13 (40) | 15 (45) | .8036 |
| Acute chest syndrome | — | 29 (45) | N/A | 9 (28) | 20 (60) | .1778 |
| Vaso-occlusive episode (at least 1 in the last 12 months) | — | 40 (62) | N/A | 17 (53) | 23 (69) | 1.000 |
| Biochemical and hematologic features | ||||||
| Hemoglobin (g/dL) | — | 9.2 [7.2-12.2] | N/A | 9.5 [7.2-12.2] | 9.0 [7.2-11.8] | .2089 |
| LDH (UI/L), median [range] | — | 348 [27-770] | N/A | 358 [27-770] | 348 [193-531] | .2403 |
| Reticulocyte count (G/L), median [range] | — | 223 [49-674] | N/A | 225 [78-674] | 223 [49-611] | .3207 |
| MCV (fl), median [range] | — | 84 [59-122] | N/A | 82 [59-93] | 86 [65-122] | .0075 |
| HbF (%), median [range] | — | 2.3 [0.4-29.1] | N/A | 1.6 [0.4-6.0] | 3.7 [0.5-29.1] | .0008 |
| HC | ||||||
| Dose (mg/kg per day), median [range] | — | 18.99 [7.14-36.11] | N/A | — | 18.99 [7.14-36.11] | N/A |
| Duration (day), median [range] | — | 2491 [140 –7154] | N/A | — | 2491 [140 –7154] | N/A |
| Transfusion program, n (%) | — | 41 (63) | N/A | 22 (69) | 19 (58) | .8155 |
| Motherhood, n (%) | — | 30 (46) | N/A | 15 (46) | 15 (45) | 1.000 |
| AMH (ng/mL), median [range] | 3.40 [0.60-17.60] | 1.51 [0.01-9.10] | < .0001 | 2.47 [0.01-9.10] | 1.31 [0.01-5.54] | .01 |
| DOR, n (%) | 9 (7) | 19 (29) | .011 | 7 (22) | 12 (36) | .27 |
| Age (y) . | Control patients (n = 130) . | Patients with SCD (n = 65) . | Patients in the non-HC group (n = 32) . | Patients in the HC group (n = 33) . | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Samples (n) . | AMH (ng/mL) Median [range] . | Percent of low values for age . | Samples (n) . | AMH (ng/mL) Median [range] . | Percent of low values for age . | P value (Fisher exact test) . | Samples (n) . | AMH (ng/mL) Median [range] . | Percent of low values for age . | P value (Fisher exact test) . | Samples (n) . | AMH (ng/mL) Median [range] . | Percent of low values for age . | P value (Fisher exact test) . | |
| [16-19] | 0 | — | N/A | 15 | 2.53 [1.30-5.75] | — | N/A | 6 | 3.10 [1.39-5.75] | — | N/A | 9 | 2.10 [1.30-2.94] | — | N/A |
| [20-24] | 32 | 3.97 [1.12-11.10] | 3.125 | 16 | 2.13 [1.00-9.10] | 43.75 | <.0001 | 8 | 3.47 [1.29-9.10] | 25.00 | < .0001 | 8 | 1.49 [1.00-4.91] | 62.50 | <.0001 |
| [25-29] | 53 | 4.00 [0.61-17.70] | 1.89 | 11 | 2.35 [0.27-4.07] | 27.27 | <.0001 | 9 | 2.55 [1.00-4.07] | 11.10 | .005 | 2 | 0.64 [0.27-1.01] | 100.00 | N/A |
| [30-34] | 24 | 2.55 [0.60-13.46] | 4.17 | 12 | 1.19 [0.01-3.65] | 33.33 | <.0001 | 7 | 0.91 [0.01-3.65] | 42.90 | < .0001 | 5 | 1.44 [0.45-2.88] | 20.00 | N/A |
| [35-39] | 17 | 2.26 [0.92-4.98] | 0 | 9 | 0.52 [0.02-2.39] | 44.44 | <.0001 | 2 | 1.21 [0.02-2.39] | 50 | N/A | 7 | 0.52 [0.22-1.24] | 42.86 | .0007 |
| 40 | 4 | 2.14 [0.90-3.08] | N/A | 2 | 0.21 [0.01-0.40] | — | N/A | 0 | — | — | N/A | 2 | 0.21 [0.01-0.40] | — | N/A |
| Age (y) . | Control patients (n = 130) . | Patients with SCD (n = 65) . | Patients in the non-HC group (n = 32) . | Patients in the HC group (n = 33) . | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Samples (n) . | AMH (ng/mL) Median [range] . | Percent of low values for age . | Samples (n) . | AMH (ng/mL) Median [range] . | Percent of low values for age . | P value (Fisher exact test) . | Samples (n) . | AMH (ng/mL) Median [range] . | Percent of low values for age . | P value (Fisher exact test) . | Samples (n) . | AMH (ng/mL) Median [range] . | Percent of low values for age . | P value (Fisher exact test) . | |
| [16-19] | 0 | — | N/A | 15 | 2.53 [1.30-5.75] | — | N/A | 6 | 3.10 [1.39-5.75] | — | N/A | 9 | 2.10 [1.30-2.94] | — | N/A |
| [20-24] | 32 | 3.97 [1.12-11.10] | 3.125 | 16 | 2.13 [1.00-9.10] | 43.75 | <.0001 | 8 | 3.47 [1.29-9.10] | 25.00 | < .0001 | 8 | 1.49 [1.00-4.91] | 62.50 | <.0001 |
| [25-29] | 53 | 4.00 [0.61-17.70] | 1.89 | 11 | 2.35 [0.27-4.07] | 27.27 | <.0001 | 9 | 2.55 [1.00-4.07] | 11.10 | .005 | 2 | 0.64 [0.27-1.01] | 100.00 | N/A |
| [30-34] | 24 | 2.55 [0.60-13.46] | 4.17 | 12 | 1.19 [0.01-3.65] | 33.33 | <.0001 | 7 | 0.91 [0.01-3.65] | 42.90 | < .0001 | 5 | 1.44 [0.45-2.88] | 20.00 | N/A |
| [35-39] | 17 | 2.26 [0.92-4.98] | 0 | 9 | 0.52 [0.02-2.39] | 44.44 | <.0001 | 2 | 1.21 [0.02-2.39] | 50 | N/A | 7 | 0.52 [0.22-1.24] | 42.86 | .0007 |
| 40 | 4 | 2.14 [0.90-3.08] | N/A | 2 | 0.21 [0.01-0.40] | — | N/A | 0 | — | — | N/A | 2 | 0.21 [0.01-0.40] | — | N/A |
Low values for age are AMH values below the reference values established for an age class. Diminished ovarian reserve is defined as an AMH level below 1.2 ng/mL.
Controls and patients were matched as 2:1 for age. The matched control population consisted of patients who were free of sickle cell disease with healthy AMH values for age, attending our institution's reproductive medicine unit for male, tubal, or unexplained infertility. Matching according to the age was carried out by staff who were aware of the matching criteria but otherwise blinded to the AMH results.
We used the Mann-Whitney or Kruskal-Wallis test with Dunn posttest to analyze quantitative variables (expressed as the median [range]) and Fisher exact test to analyze categorical variables.
BMI, body mass index; DOR, diminished ovarian reserve; HbF, fetal hemoglobin; LDH, lactate dehydrogenase; MCV, mean corpuscular volume; SCD, sickle cell disease.