A total of 91 cycles of 19 patients with POI were analyzed in this study. Out of the total of 19 patients, four had histories of chemotherapy, three had a documented chromosomal abnormality, and 12 patients lacked a definitive cause for the POI. Out of these 12 patients, seven were positive for thyroid autoantibodies (TPOAb and/or TgAb). Table 1 shows the patient characteristics categorized by positive or negative serum AMH measured using the picoAMH kits. The median age of onset of POI did not differ between the negative and positive AMH groups. All of the patients with one or more AMH-positive cycles experienced follicle growth during the observation periods. In contrast, out of the group of patients who were AMH-negative, only 14.3% experienced follicle growth (Table 1).
Table 1. Comparison According to Serum AMH in patients with POI.
Variable
|
Overall (n = 19)
|
AMH-negative (n = 14)
|
AMH-positive (n = 5)
|
p-value b
|
Age at onset of POI (years)
|
17.0 (15.0, 23.0)
|
16.0 (14.0, 20.0)
|
22.0 (17.0, 27.0)
|
0.876 c
|
Age at first observation period (years)
|
25.2 (23.4, 30.8)
|
24.8 (20.7, 31.2)
|
27.6 (24.7, 33.4)
|
0.3913 c
|
Serum FSH a (mIU/mL)
|
46.4 (22.7, 70.5)
|
46.4 (33.1, 75.3)
|
66.2 (13.2, 78.5)
|
0.9644 c
|
Follicle growth, n (%)
|
7 (37)
|
2 (14)
|
5 (100)
|
0.0018 d
|
AMH, anti-Müllerian hormone; POI, primary ovarian insufficiency; FSH, follicle-stimulating hormone
AMH-positive, patients with one or more AMH-positive cycles
AMH-negative, patients without AMH-positive cycles
Follicle growth, number of patients with a history of follicle growth in one or more of the observation periods
Values are presented as median (25th, 75th percentile)
a Serum FSH levels at first observation period.
b Compare AMH-positive and negative groups.
c Mann–Whitney U test
d Fisher's exact test
For the purpose of evaluating AMH as a predictive factor for follicle growth of the cycle, we analyzed the serum levels of AMH and FSH and the follicle growth of each cycle. Of the total 91 cycles, 14 were positive for AMH, and 14 cycles presented with follicle growth. The serum FSH levels of the cycles with follicle growth were significantly lower, and the serum AMH levels significantly higher, than those in cycles without follicle growth (Figure 1). The median serum FSH and AMH levels of cycles with follicle growth were 15.44 mIU/mL (25th, 75th percentile: 5.03, 26.85) and 2.77 pg/mL (25th, 75th percentile: 0.0, 9.64), respectively. Out of the 14 AMH-positive cycles, nine presented with follicle growth, and five did not show follicle growth. However, of these five cycles, two were positive for AMH in the previous cycles. Serum FSH levels in the AMH-positive cycles were significantly lower than in the AMH-negative cycles (Table 2).
Table 2. Serum AMH and FSH and follicle growth in AMH-positive or negative cycles.
Variable
|
AMH-negative
(n = 77)
|
AMH-positive
(n = 14)
|
p-value
|
Serum FSH (mIU/mL)
|
33.0 (20.4–49.0)
|
10.0 (5.0–26.6)
|
0.0058 a
|
Serum AMH (pg/mL)
|
0.0 (0.0–0.0)
|
7.7 (4.6–22.3)
|
<0.0001 a
|
Follicle growth, n (%)
|
5 (6)
|
9 (64)
|
<0.0001 b
|
AMH, anti-Müllerian hormone; FSH, follicle-stimulating hormone
Values are presented as median (25th, 75th percentile)
a Mann–Whitney U test
b Fisher's exact test
The positive predictive value (PPV) and negative predictive value (NPV) of AMH-positive serum for follicle growth of the cycle were 0.643 and 0.935, respectively. At the same time, we assessed the usefulness of serum FSH levels in the prediction of follicle growth. When we set FSH levels < 10 mIU/mL as a predictor of follicle growth, the PPV of FSH was 0.250 and the NPV was 0.873. These results indicate that AMH-positive serum during the withdrawal period is superior to low levels of serum FSH as a predictor of follicle growth in the cycle.