Clinical characteristics
A total of 140 women with unexplained recurrent miscarriage were included in this study. The age of the participants ranged from 19 to 43 years. Among them, 106 (75.71%) women were assigned to the ongoing pregnancy group. Additionally, 34 (24.29%) women suffered from miscarriage and were included in the miscarriage group. There were no significant differences between the two groups in terms of age (P = 0.498), gravidity (P = 0.316), parity (P = 0.604), miscarriage (P = 0.395), or cesarean section (P = 1.000). The characteristics of the two groups are summarized in Table 1.
Table 1
Clinical data of the study population.
Characteristics | Ongoing pregnancy (n = 106) | Miscarriage (n = 34) | P |
Age, years | 31.42 ± 3.91 | 31.76 ± 4.45 | 0.498 |
Gravidity | | | |
2 | 51(48.11) | 14(41.18) | 0.316 |
3 | 34(32.08) | 9(26.47) | |
>=4 | 21(19.81) | 11(32.35) | |
Parity | | | |
0 | 66(62.26) | 21(61.76) | 0.604 |
1 | 35(33.02) | 10(29.41) | |
>=2 | 5(4.72) | 3(8.82) | |
Number of miscarriages | | | |
2 | 78(73.59) | 22(64.71) | 0.395 |
3 | 18(16.98) | 6(17.65) | |
>=4 | 10(9.43) | 6(17.65) | |
Previous cesarean section | | | |
Yes | 9(8.49) | 2(5.88) | 1.000 |
No | 97(91.51) | 32(94.12) | |
Continuous data were presented as the mean ± SD, and categorical data were presented as count and percentage.
Serum β-hCG, E2, and Prog at different gestational weeks and changes in their absolute values over time per patient
We compared serum β-hCG, E2, and Prog levels by week between the two groups. Table 2 shows that at the 3-5th week of pregnancy, the serum β-hCG and E2 levels of the miscarriage group and the ongoing pregnancy group had no remarkable differences in the statistical analysis, whereas from the 6th week to 10th week, the serum β-hCG and E2 levels of the ongoing pregnancy group were significantly higher than those of the miscarriage group. The changes in serum β-hCG, E2, and Prog levels over the indicated weeks are presented in Fig. 1. The changes in the absolute values of serum β-hCG, E2, and Prog levels over time per patient are shown in Fig. 2.
Table 2. Comparison of serum β-hCG, E2, and Prog levels between the ongoing pregnancy group and miscarriage group
Gestational week
|
Case number
|
β-HCG (mIU/ml)
|
E2 (pg/mL)
|
Prog (ng/ml)
|
Ongoing pregnancy
|
Miscarriage
|
Ongoing pregnancy
|
Miscarriage
|
P
|
Ongoing pregnancy
|
miscarriage
|
P
|
Ongoing pregnancy
|
Miscarriage
|
P
|
Median
|
IQR
|
Median
|
IQR
|
Median
|
IQR
|
Median
|
IQR
|
Median
|
IQR
|
Median
|
IQR
|
3rd
|
11
|
7
|
111.57
|
106.2
|
165
|
1046.50
|
0.375
|
237
|
183
|
221
|
129
|
0.328
|
24.41
|
8.87
|
27.48
|
12.90
|
0.179
|
4th
|
60
|
22
|
1718.50
|
3046.79
|
1886.50
|
5255.95
|
0.457
|
347.5
|
246.5
|
337
|
132
|
0.241
|
23.58
|
10.03
|
19.41
|
10.11
|
0.003
|
5th
|
81
|
26
|
10339
|
18604.50
|
8246.50
|
9257.25
|
0.212
|
448
|
301
|
427
|
272
|
0.839
|
22.75
|
13.97
|
18.02
|
7.39
|
0.058
|
6th
|
80
|
25
|
46368
|
62029
|
17623
|
21173.50
|
0.001
|
594
|
473.75
|
408
|
242
|
0.001
|
20.1
|
10.17
|
17.08
|
10.18
|
0.068
|
7th
|
50
|
16
|
98606
|
103261
|
24717.50
|
54137.50
|
<0.001
|
721.5
|
526
|
361.3
|
294.25
|
<0.001
|
16
|
8.54
|
12.26
|
10.59
|
0.006
|
8th-10th
|
36
|
6
|
140418.50
|
69979.75
|
51042
|
80467.25
|
<0.001
|
1106
|
1105.25
|
638.50
|
452.50
|
0.012
|
17.44
|
5.32
|
18.92
|
10.55
|
0.875
|
β-hCG, β-human chorionic gonadotropin; E2, estradiol; Prog, progesterone; IQR, interquartile range.
ROC analyses to determine the cutoff value of Δβ-hCG, ΔE2, and ΔProg in predicting pregnancy outcome
We calculated the weekly changes in serum hormone levels (Δβ-hCG, ΔE2, and ΔProg) and found that Δβ-hCG (ongoing pregnancy: median: 37,989.700 mIU/ml, IQR: 35,109.168 mIU/ml; miscarriage: median: 8612.778 mIU/ml, IQR:15821.517 mIU/ml; P < 0.001) and ΔE2 (ongoing pregnancy: median: 217.194 pg/ml, IQR: 258.562 pg/ml; miscarriage: median: 23.72 pg/ml, IQR: 121.674 pg/ml; P < 0.001) were significantly different between the two groups and may be correlated with pregnancy outcomes during the follow-up period; however, ΔProg was not significantly different (ongoing pregnancy: median: -0.471 ng/ml, IQR: 4.745 ng/ml; miscarriage: median: -0.498 ng/ml, IQR: 5.405 ng/ml; P = 0.825). The ROC curves of Δβ-hCG, ΔE2, and ΔProg for achieving ongoing pregnancy at the 20th gestational age are shown in Fig. 3. For Δβ-hCG, the cutoff value was 30,632.855 mIU/ml, with the corresponding Youden index being 0.612, and the area under the curve was 0.841 and notably accurate for predicting ongoing pregnancy. For ΔE2, the cutoff value was 45.055 pg/ml, with the corresponding Youden index being 0.621, and the area under the curve was 0.839 and notably accurate for predicting ongoing pregnancy. For ΔProg, the cutoff value was − 2.216 ng/ml, with the corresponding Youden index being 0.119, and the area under the curve was 0.513 and hardly accurate for predicting ongoing pregnancy. (Table 3)
Table 3
Cutoff points β-hCG, E2, and Prog levels and performance for predicting pregnancy outcomes.
Performance | β-hCG | E2 | Prog |
Cutoff | 30632.855 mIU/ml | 45.055 pg/ml | -2.2155 ng/ml |
Accuracy(95% CI) | 0.721(0.638–0.792) | 0.864(0.794–0.914) | 0.636(0.550–0.714) |
Sensitivity(95% CI) | 0.971(0.829–0.998) | 0.706(0.523–0.843) | 0.412(0.251–0.592) |
Specificity(95% CI) | 0.642(0.542–0.731) | 0.915(0.841–0.958) | 0.708(0.610–0.790) |
PPV(95% CI) | 0.465(0.347–0.586) | 0.727(0.542–0.861) | 0.311(0.186–0.468) |
NPV(95% CI) | 0.986(0.911–0.999) | 0.907(0.831–0.952) | 0.789(0.691–0.863) |
AUC(95% CI) | 0.841(0.769–0.914) | 0.839(0.752–0.926) | 0.513(0.402–0.623) |
Youden Index | 0.612 | 0.621 | 0.119 |
β-hCG, β-human chorionic gonadotropin; E2, estradiol; Prog, progesterone; PPV, positive predictive value; NPV, negative predictive value; AUC, area under curve; CI, confidence interval. |