A total of 1122 patients were retrospectively enrolled in the study. We followed up one year and obtained information on the clinical pregnancy outcomes of them. 129 patients (15.6%) were diagnosed with CSD (mean length: 0.42±0.21 cm, mean width: 0.38±0.17 cm, and mean depth: 0.70±0.14 cm). Among the 409 patients who underwent SET, 300 had previous CD, 54 had previous VD, and 55 had a CSD. Their demographics and cycle characteristics are presented in Table 1. There were no significant differences in these variables between the three SET groups, except for age between groups A1 and C1. Among the remaining 713 patients who underwent DET, 400 had previous CD, 239 had previous VD, and 74 had a CSD. Their demographics and cycle characteristics are presented in Table 2. The three DET groups exhibited significant differences in age, infertility duration, and basal FSH.
Table 1 Demographics and cycle characteristics in single embryo transfer (SET) groups (n=409)
|
|
|
|
P
|
|
A1(n=300)
|
B1(n=54)
|
C1(n=55)
|
A1&B1
|
A1&C1
|
B1&C1
|
T P
|
Age (years)
|
33.5±3.7
|
33.8±3.9
|
34.9±4.7
|
0.5911
|
0.0151
|
0.1901
|
0.0511
|
Body Mass Index (kg/m2)
|
23.4±3.2
|
23.2±2.9
|
23.6±3.0
|
0.6301
|
0.7321
|
0.5051
|
0.8131
|
Duration of infertility (years)
|
4.2±3.1
|
5.1±3.2
|
4.4±3.2
|
0.0721
|
0.7461
|
0.2721
|
0.2001
|
Infertility diagnosis,n(%)
|
|
|
|
0.7452
|
0.1762
|
0.5672
|
0.4612
|
Male factor
|
47 (15.7)
|
9 (16.7)
|
4 (7.3)
|
|
|
|
|
Tubal factor
|
118 (39.3)
|
18 (33.3)
|
17 (30.9)
|
|
|
|
|
Other
|
75 (25.0)
|
12 (22.2)
|
17 (30.9)
|
|
|
|
|
Unexplained
|
7 (2.3)
|
2 (3.7)
|
2 (3.6)
|
|
|
|
|
Combined
|
53 (17.7)
|
13 (24.1)
|
15 (27.3)
|
|
|
|
|
Endometrial preparation,n(%)
|
|
|
|
0.9922
|
0.8732
|
0.9092
|
0.9872
|
Modified natural cycle
|
178 (59.3)
|
32 (59.3)
|
32 (58.2)
|
|
|
|
|
HRT
|
122 (40.7)
|
22 (40.7)
|
23 (41.8)
|
|
|
|
|
Basal FSH (mIU/L)
|
6.4±2.1
|
6.1±2.4
|
6.7±1.9
|
0.3791
|
0.3111
|
0.1591
|
0.3501
|
Basal LH (mIU/L)
|
4.3±2.7
|
3.9±2.7
|
4.0±1.9
|
0.2971
|
0.4371
|
0.7951
|
0.4631
|
Basal E2 (mIU/L)
|
44.7±24.3
|
40.1±16.3
|
48.4±33.2
|
0.1771
|
0.3301
|
0.0991
|
0.2131
|
No. oocytes retrieved
|
17.6±8.5
|
17.2±8.7
|
17.5±10.5
|
0.7361
|
0.9501
|
0.8961
|
0.9461
|
High-quality embryo rate
|
25.0±42.9
|
21.3±39.6
|
26.2±34.7
|
0.5591
|
0.8441
|
0.4991
|
0.8011
|
Stage of embryo
|
|
|
|
0.9272
|
0.5352
|
0.5762
|
0.8112
|
Cleavage
|
246(82.0)
|
44(81.5)
|
47(85.5)
|
|
|
|
|
Blastocyst
|
54(18.0)
|
10(18.5)
|
8(14.5)
|
|
|
|
|
E2: estradiol; FSH: follicle-stimulating hormone; LH: luteinizing hormone; A1: previous cesarean delivery (CD) and single embryo transfer (SET); B1: previous vaginal delivery (VD) and SET; C1: cesarean scar defect (CSD) and SET. Data are mean±SD unless stated otherwise.
1 One-way analysis of variance. 2 Pearson’s χ2 test.
Table 2 Demographics and cycle characteristics in double embryo transfer (DET) groups (n=713)
|
|
|
|
P
|
|
A2(n=400)
|
B2(n=239)
|
C2(n=74)
|
A2&B2
|
A2&C2
|
B2&C2
|
T P
|
Age (years)
|
33.7±3.4
|
34.3±3.5
|
35.5±5.2
|
0.0311
|
<0.0011
|
0.0241
|
0.0001
|
Body Mass Index (kg/m2)
|
23.1±3.1
|
22.8±2.9
|
22.5±3.9
|
0.4331
|
0.1911
|
0.4101
|
0.3621
|
Duration of infertility (years)
|
4.2±3.1
|
4.8±3.3
|
4.5±3.2
|
0.0141
|
0.3861
|
0.5141
|
0.0481
|
Infertility diagnosis,n(%)
|
|
|
|
0.0752
|
0.8432
|
0.7942
|
0.3202
|
Male factor
|
70 (17.5)
|
38 (15.9)
|
10 (13.5)
|
|
|
|
|
Tubal factor
|
137 (34.4)
|
101 (42.3)
|
28 (37.8)
|
|
|
|
|
Other
|
105 (26.3)
|
55 (23.0)
|
21 (28.4)
|
|
|
|
|
Unexplained
|
12 (3.0)
|
13 (5.4)
|
3 (4.1)
|
|
|
|
|
Combined
|
76 (19.8)
|
32 (13.4)
|
12 (16.2)
|
|
|
|
|
Endometrial preparation,n(%)
|
|
|
|
0.8512
|
0.9762
|
0.9312
|
0.9822
|
Modified natural cycle
|
244 (61.0)
|
144 (60.3)
|
45 (60.8)
|
|
|
|
|
HRT
|
156 (39.0)
|
95 (39.7)
|
29 (39.2)
|
|
|
|
|
Basal FSH (mIU/L)
|
6.5±1.8
|
6.3±2.1
|
6.9±2.2
|
0.1121
|
0.1331
|
0.0361
|
0.0531
|
Basal LH (mIU/L)
|
4.0±2.2
|
3.9±1.8
|
3.5±1.4
|
0.7021
|
0.0891
|
0.0971
|
0.2081
|
Basal E2 (mIU/L)
|
43.4±26.2
|
46.4±20.2
|
45.4±20.2
|
0.1511
|
0.5321
|
0.5821
|
0.3071
|
No. oocytes retrieved
|
16.9±7.3
|
16.9±7.4
|
15.0±6.1
|
0.9201
|
0.1041
|
0.0991
|
0.2441
|
High-quality embryo rate
|
26.0±37.3
|
32.4±41.7
|
33.7±29.1
|
0.0511
|
0.1081
|
0.8131
|
0.0771
|
Stage of embryo
|
|
|
|
0.3742
|
0.4372
|
0,8712
|
0.5832
|
Cleavage
|
377(94.3)
|
221(92.5)
|
68(91.9)
|
|
|
|
|
Blastocyst
|
23(5.8)
|
18(7.5)
|
6(8.1)
|
|
|
|
|
E2: estradiol; FSH: follicle-stimulating hormone; LH: luteinizing hormone; A2: previous cesarean delivery (CD) and double embryo transfer (DET); B2: previous vaginal delivery (VD) and DET; C2: cesarean scar defect and DET.
1 One-way analysis of variance. 2 Pearson’s χ2 test.
The results of the unadjusted analyses are shown in Tables 3 and 4. In SET patients (Table 3), the clinical pregnancy and live birth rates decreased in C1 (27.3% and 23.6%, respectively) compared to in group B1 (44.4% and 35.2%, respectively) or group A1 (39.0% and 30.3%, respectively), but there were no significant differences in any of the pregnancy outcomes among the three SET groups (P>0.05), except for neonatal birth weight. In contrast, in DET patients (Table 4), the clinical pregnancy and live birth rates were significantly lower in group C2 (33.8% and 24.3%, respectively) compared to in group A2 (46.8% and 36.8%, respectively) or in group B2 (59.8% and 49.4%, respectively), and in group A2 compared to group B2 (P<0.05). Moreover, in DET patients, the multiple pregnancy rate was significantly lower in group A2 (10.8%) and C2 (9.5%) than group B2 (20.1%) (P<0.05 for both). In the DET patients, ectopic pregnancies only occurred in group A2, which had five cases. There were no significant differences in pregnancy loss rate, pregnancy complication rate, preterm birth rate, or neonatal birth weight among the three DET groups (P>0.05).
Table 3 Single embryo transfer (SET) reproductive outcomes (unadjusted analysis)
|
|
|
|
P
|
|
A1 (n=300)
|
B1 (n=54)
|
C1 (n=55)
|
A1 vs. B1
|
A1 vs. C1
|
B1 vs. C1
|
T P
|
Clinical pregnancy, n (%)
|
117 (39.0)
|
24 (44.4)
|
15 (27.3)
|
0.4521
|
0.0981
|
0.0611
|
0.1531
|
Pregnancy loss, n (%)
|
22 (18.8)
|
3 (12.5)
|
2 (13.3)
|
0.4611
|
0.6051
|
0.9401
|
0.6921
|
Early pregnancy loss, n (%)
|
20 (17.1)
|
3 (12.5)
|
2 (13.3)
|
0.5791
|
0.7131
|
0.9401
|
0.8181
|
Late pregnancy loss, n (%)
|
2 (1.7)
|
0
|
0
|
0.5191
|
0.6101
|
NA
|
0.7131
|
Ectopic pregnancy, n (%)
|
3 (2.6)
|
1 (4.2)
|
0
|
0.6671
|
0.5301
|
0.4231
|
0.7261
|
Pregnancy complications, n (%)
|
18 (15.4)
|
5 (20.8)
|
0
|
0.5101
|
0.1021
|
0.0581
|
0.1881
|
Preterm birth, n (%)
|
12 (13.2)
|
4 (21.1)
|
2 (15.4)
|
0.3761
|
0.8281
|
0.6871
|
0.6751
|
Live birth, n (%)
|
91 (30.3)
|
19 (35.2)
|
13 (23.6)
|
0.4781
|
0.3161
|
0.1861
|
0.4141
|
LBW, n (%)
|
6 (6.6)
|
0
|
0
|
0.2501
|
0.3401
|
NA
|
0.3301
|
NBW, n (%)
|
74 (81.3)
|
12 (63.2)
|
13 (100)
|
0.0811
|
0.0881
|
0.0131
|
0.0331
|
HBW, n (%)
|
11 (12.1)
|
7 (36.8)
|
0
|
0.0081
|
0.1851
|
0.0131
|
0.0061
|
LBW: low birth weight; HBW: high birth weight; NBW: normal birth weight.
1Pearson’s χ2 test
Table 4 Double embryo transfer (DET) reproductive outcomes (unadjusted analysis)
|
|
|
|
P
|
|
A2 (n=400)
|
B2 (n=239)
|
C2 (n=74)
|
A2 vs. B2
|
A2 vs. C2
|
B2 vs. C2
|
T P
|
Clinical pregnancy, n (%)
|
187 (46.8)
|
143 (59.8)
|
25 (33.8)
|
0.0011
|
0.0391
|
<0.0011
|
<0.0011
|
Multiple pregnancy, n (%)
|
43 (10.8)
|
48 (20.1)
|
7 (9.5)
|
0.0011
|
0.7401
|
0.0361
|
0.0021
|
Pregnancy loss, n (%)
|
33 (17.6)
|
24 (16.8)
|
7 (28.0)
|
0.8371
|
0.2141
|
0.1821
|
0.3961
|
Early pregnancy loss, n (%)
|
27 (14.4)
|
18 (12.6)
|
6 (24.0)
|
0.6271
|
0.2161
|
0.1321
|
0.3241
|
Late pregnancy loss, n (%)
|
6 (3.2)
|
6 (4.2)
|
1 (4.0)
|
0.6351
|
0.8351
|
0.9641
|
0.8901
|
Ectopic pregnancy, n (%)
|
5 (2.7)
|
0
|
0
|
0.0491
|
0.4081
|
NA
|
0.1021
|
Pregnancy complications, n (%)
|
36 (19.3)
|
21 (14.7)
|
5 (20.0)
|
0.2771
|
0.9291
|
0.4981
|
0.5241
|
Preterm birth, n (%)
|
33 (22.4)
|
20 (16.9)
|
6 (33.3)
|
0.2661
|
0.3051
|
0.1001
|
0.2211
|
Live birth, n (%)
|
147 (36.8)
|
118 (49.4)
|
18 (24.3)
|
0.0021
|
0.0391
|
<0.0011
|
<0.0011
|
LBW, n (%)
|
23 (13.5)
|
26 (17.3)
|
4 (20.0)
|
0.3461
|
0.4331
|
0.7691
|
0.5511
|
NBW, n (%)
|
137 (80.6)
|
114 (76.0)
|
15 (75.0)
|
0.3191
|
0.5551
|
0.9221
|
0.5721
|
HBW, n (%)
|
10 (5.9)
|
10 (6.7)
|
1 (5.0)
|
0.7721
|
0.8731
|
0.7761
|
0.9351
|
LBW: low birth weight; HBW: high birth weight; NBW: normal birth weight.
1 Pearson’s χ2 test.
Logistic regression was performed to determine the effects of previous CD and CSD on clinical pregnancy, multiple pregnancy, pregnancy loss, preterm birth, and live birth while adjusting for age, pre-pregnancy BMI, infertility duration, infertility diagnosis, endometrial preparation, basal FSH, basal LH, basal E2, number of oocytes retrieved, and high-quality embryo rate as potential confounders. The results are presented in Tables 5. In SET patients, CSD (compared to previous VD) was associated with a significantly lower clinical pregnancy rate (adjusted OR 0.31, 95% CI: 0. 12–0. 81, P=0.017). In DET patients, previous CD (compared to previous VD) was associated with a significantly lower clinical pregnancy rate (adjusted OR 0. 56, 95% CI: 0. 40–0. 79, P=0.001), multiple pregnancy rate (adjusted OR 0. 42, 95% CI: 0. 26–0. 68, P=0.001), and live birth rate (adjusted OR 0. 57, 95% CI: 0. 41–0. 81, P=0.001). Additionally, in DET patients, CSD (compared to previous VD) was associated with a significantly lower clinical pregnancy rate (adjusted OR 0. 39, 95% CI: 0. 21–0.72, P=0.002) and live birth rate (adjusted OR 0. 37, 95% CI: 0. 20–0. 70, P=0.002). Previous CD and CSD were not significantly associated with pregnancy complications, pregnancy loss, or preterm birth.
Table 5 Multivariate logistic regression analysis for the patients of following frozen embryo transfer.
|
A1(n=409)
|
A2(n=713)
|
C1(n=409)
|
C2(n=713)
|
|
OR (95%CI)
|
P
|
OR (95%CI)
|
P
|
OR (95%CI)
|
P
|
OR (95%CI)
|
P
|
Clinical pregnancy
|
0.74 (0.40-1.36)
|
0.331
|
0.56 (0.40-0.79)
|
0.001
|
0.31 (0.12-0.81)
|
0.017
|
0.39 (0.21-0.72)
|
0.002
|
Multiple pregnancy
|
NA
|
NA
|
0.42 (0.26-0.68)
|
<0.001
|
NA
|
NA
|
0.47 (0.19-1.15)
|
0.098
|
Pregnancy loss
|
1.65 (0.43-6.29)
|
0.464
|
1.05 (0.58-1.90)
|
0.876
|
0.03 (0.00-15.59)
|
0.273
|
1.97 (0.71-5.47)
|
0.193
|
Early pregnancy loss
|
1.46 (0.38-5.58)
|
0.582
|
1.15 (0.59-2.24)
|
0.678
|
0.03 (0.00-15.59)
|
0.273
|
2.22 (0.73-6.74)
|
0.159
|
Late pregnancy loss
|
NA
|
NA
|
0.77 (0.24-2.49)
|
0.658
|
NA
|
NA
|
1.36 (0.14-13.47)
|
0.793
|
Pregnancy complications
|
NA
|
NA
|
1.30 (0.70-2.39)
|
0.407
|
NA
|
NA
|
2.07 (0.63-6.74)
|
0.228
|
Live birth
|
0.75 (0.39-1.42)
|
0.370
|
0.57 (0.41-0.81)
|
0.001
|
0.48 (0.18-1.27)
|
0.140
|
0.37 (0.20-0.70)
|
0.002
|
Preterm birth
|
0.67 (0.17-2.61)
|
0.559
|
1.26 (0.67-2.39)
|
0.476
|
0.82 (0.04-18.88)
|
0.900
|
1.61 (0.42-6.13)
|
0.484
|
A1:cesarean delivery of single embryo transfer, A2:cesarean delivery of double embryo transfer, C1:previous cesarean scar defect of single embryo transfer, C2:previous cesarean scar defect of double embryo transfer,PCSD of double embryo transfer.