A total of 574 cycles (155 in GH group, 419 in Control group) were available for analysis. Basal characteristics between the two groups were listed in table 1. In terms of age (35.88±5.76vs. 34.10±4.99, P﹤
0.05), basal FSH (10.41±4.06vs. 9.59±3.51, P﹤0.05), AFC (4.42±2.15vs. 4.87±2.13, P﹤0.05), there were significant differences between two groups, the rest such as BMI, duration of infertility, AMH, basal LH and basal E2 were not different significantly. In stratified analysis, the variables of G4(100 in GH group, 172 in Control group) were not significantly different, and in G3(55 in GH group, 247 in Control group), age (29.20±2.77vs. 30.72±2.71, P﹤0.05) was significantly different. The above mentioned significant differences, we would use linear regression and logistic regression to control them and analyzed the effect of GH.
As to the cycle characteristics and clinical outcomes(table 2), there were no differences between GH and control group, in aspects of HMG dosage, duration of HMG, the number of oocytes retrieved, the number of 2PN, the number of embryos, transferrable embryos ,good-quality embryos, clinical pregnancy rate, miscarriage rate and clinical live birth rate. In stratified analysis, the variables of G4 were not significantly different, and in G3, duration of HMG (8.11±1.86vs. 8.80±1.98, P﹤0.05) was significantly different, which means for POR patients who were younger than 35 years old, GH may reduce the stimulation time.
Linear regression and logistic regression were played to clarify the real effect of GH on patients (table 3). In group all and G4, there were no significant differences between GH group and control group in HMG dosage, duration of HMG, the number of oocytes retrieved, the number of 2PN, the number of embryos, transferrable embryos ,good-quality embryos, clinical pregnancy rate, miscarriage rate and live birth rate. Only in G3, duration of HMG(β=-0.71, 95%CI(-1.28,0.13), P﹤0.05) was significantly reduced after GH addition. The above results show that for POR patients who were younger than 35 years old, GH adjuvant may reduce the stimulation time, while GH adjuvant may not bring beneficial effects in other aspects such as good-quality embryos, clinical pregnancy rate and live birth rate etc.
Table 1 Basal characteristics of different groups of patients.
|
all
|
G3
|
G4
|
GH(n=155)
|
Control(n=419)
|
P
|
GH(n=55)
|
control(n=247)
|
P
|
GH(n=100)
|
control(n=172)
|
P
|
Age(years)
|
35.88±5.76
|
34.10±4.99
|
0*
|
29.20±2.77
|
30.72±2.71
|
0*
|
39.54±3.05
|
38.96±3.12
|
0.139
|
BMI(kg/m2)
|
22.97±2.90
|
22.85±3.21
|
0.685
|
22.54±2.95
|
22.44±3.39
|
0.844
|
23.20±2.85
|
23.43±2.85
|
0.527
|
Duration of infertilty(years)
|
4.29±3.73
|
4.38±3.45
|
0.795
|
4.04±2.38
|
4.01±2.54
|
0.938
|
4.43±4.31
|
4.91±4.45
|
0.39
|
AMH(ng/ml)
|
0.66±0.30
|
0.71±0.30
|
0.066
|
0.78±0.26
|
0.74±0.29
|
0.345
|
0.59±0.31
|
0.67±0.30
|
0.047*
|
FSH(IU/L)
|
10.41±4.06
|
9.59±3.51
|
0.018*
|
9.13±3.02
|
9.25±3.34
|
0.807
|
11.11±4.38
|
10.09±3.69
|
0.041*
|
LH(IU/L)
|
3.94±1.82
|
3.73±1.62
|
0.179
|
3.69±1.61
|
3.57±1.74
|
0.606
|
4.08±1.92
|
3.97±1.42
|
0.606
|
E2(pg/ml)
|
42.89±17.91
|
41.96±17.64
|
0.578
|
48.03±18.75
|
42.16±18.42
|
0.034
|
40.06±16.86
|
41.68±16.50
|
0.441
|
AFC(n)
|
4.42±2.15
|
4.87±2.13
|
0.027*
|
4.96±2.25
|
5.11±2.16
|
0.645
|
4.12±2.05
|
4.51±2.05
|
0.13
|
Table 2 Cycle characteristics and clinical outcomes of different groups of patients.
|
all
|
G3
|
G4
|
GH(n=155)
|
control(n=419)
|
P
|
GH(n=55)
|
control(n=247)
|
P
|
GH(n=100)
|
control(n=172)
|
P
|
Duration of HMG(days)
|
8.53±2.06
|
8.70±2.13
|
0.399
|
8.11±1.86
|
8.80±1.98
|
0.02*
|
8.76±2.14
|
8.56±2.33
|
0.479
|
Dosage of HMG( IU)
|
1682.90±619.71
|
1701.61±602.60
|
0.743
|
1579.09±506.91
|
1682.59±555.67
|
0.206
|
1740.00±669.29
|
1728.92±664.97
|
0.895
|
Oocytes retrieved(n)
|
2.97±2.54
|
3.40±2.59
|
0.077
|
3.35±2.70
|
3.89±2.79
|
0.562
|
2.60±2.38
|
2.70±2.08
|
0.724
|
2PN(n)
|
2.05±1.91
|
2.25±2.00
|
0.284
|
2.62±2.09
|
2.52±2.14
|
0.753
|
1.74±1.74
|
1.87±1.71
|
0.56
|
embryos(n)
|
2.03±1.94
|
2.27±2.04
|
0.194
|
2.65±2.20
|
2.55±2.20
|
0.761
|
1.68±1.69
|
1.87±1.71
|
0.386
|
Transferrable embryos(n)
|
1.38±1.51
|
1.62±1.66
|
0.124
|
1.53±1.71
|
1.78±1.76
|
0.346
|
1.30±1.39
|
1.39±1.49
|
0.625
|
Good-quality embryos(n)
|
1.09±1.44
|
1.28±1.44
|
0.153
|
1.24±1.71
|
1.35±1.50
|
0.614
|
1.01±1.28
|
1.19±1.34
|
0.258
|
Clinical pregnancy(%)
|
38(24.52%)
|
121(28.88%)
|
0.3
|
18(32.73%)
|
90(36.44%)
|
0.604
|
20(20.00%)
|
31(18.02%)
|
0.687
|
Miscarriage(%)
|
9(5.81%)
|
24(5.73%)
|
0.971
|
1(1.82%)
|
13(5.26%)
|
0.272
|
8(8.00%)
|
11(6.40%)
|
0.617
|
Live birth(%)
|
29(18.71%)
|
97(23.15%)
|
0.254
|
17(30.91%)
|
77(31.17%)
|
0.969
|
12(12.00%)
|
20(11.63%)
|
0.927
|
Table 3 Linear regression and logistic regression analysis.
group
|
|
β/OR
|
95%CI
|
P
|
all
|
Duration of HMG
|
-0.21
|
(-0.59-0.18)
|
0.304
|
Dosage of HMG
|
-39.6
|
(-143.48-64.28)
|
0.454
|
Oocytes retrieved
|
-0.01
|
(-0.43-0.42)
|
0.977
|
2PN
|
0.07
|
(-0.27-0.41)
|
0.697
|
embryos
|
0.02
|
(-0.33-0.37)
|
0.919
|
Transferrable embryos
|
-0.08
|
(-0.37-0.21)
|
0.588
|
Good-quality embryos
|
-0.09
|
(-0.35-0.17)
|
0.48
|
Clinical pregnancy
|
1.02
|
(0.65-1.60)
|
0.947
|
Miscarriage
|
0.88
|
(0.39-2.00)
|
0.763
|
Live birth
|
1.02
|
(0.62-1.69)
|
0.946
|
G3
|
Duration of HMG
|
-0.71
|
(-1.28-0.13)
|
0.016*
|
Dosage of HMG
|
-119.88
|
(-270.31-30.55)
|
0.118
|
Oocytes retrieved
|
-0.19
|
(-0.96-0.59)
|
0.634
|
2PN
|
0.27
|
(-0.33-0.87)
|
0.376
|
embryos
|
0.26
|
(-0.37-0.89)
|
0.413
|
Transferrable embryos
|
-0.15
|
(-0.66-0.36)
|
0.572
|
Good-quality embryos
|
-0.05
|
(-0.50-1.97)
|
0.986
|
Clinical pregnancy
|
1.5
|
(0.61-3.71)
|
0.381
|
Miscarriage
|
0.63
|
(0.07-5.60)
|
0.678
|
Live birth
|
1.05
|
(0.53-2.11)
|
0.884
|
G4
|
Duration of HMG
|
0.13
|
(-0.43-0.68)
|
0.66
|
Dosage of HMG
|
11.56
|
(-142.30-165.42)
|
0.882
|
Oocytes retrieved
|
0.19
|
(-0.29-0.66)
|
0.44
|
2PN
|
0.05
|
(-0.35-0.46)
|
0.803
|
embryos
|
-0.14
|
(-0.42-0.39)
|
0.944
|
Transferrable embryos
|
0.05
|
(-0.30-0.40)
|
0.782
|
Good-quality embryos
|
-0.06
|
(-0.39-0.26)
|
0.693
|
Clinical pregnancy
|
1.65
|
(0.83-3.30)
|
0.153
|
Miscarriage
|
1.42
|
(0.53-3.78)
|
0.484
|
Live birth
|
1.84
|
(0.76-4.50)
|
0.178
|
Given that in our reproductive medicine center, we don’t add GH as a regular treatment principle in the first cycle, if the first cycle failed, we consider to add GH in the next cycle. So we exclude those first cycles of each group to reanalyze the effect of GH on non-first cycles.
A total of 274 cycles (122 in GH group, 152 in Control group) were analyzed. Basal characteristics between the two groups of non-first cycles were listed in table 4. There were no significant differences between two groups in age, BMI, duration of infertility, AMH, basal FSH, basal LH and basal E2. In stratified analysis, the variables of G4’(74 in GH group,71 in Control group) were not significantly different, and in G3’(48 in GH group, 81 in Control group), age (29.17±2.82 vs. 30.79±2.77, P﹤0.05) was significantly different.
Table 5 shows the cycle characteristics and clinical outcomes of non-first cycle patients, there were no differences between GH group and control group, in aspects of HMG dosage, duration of HMG, the number of oocytes retrieved, the number of 2PN, the number of embryos, transferrable embryos ,good-quality embryos, clinical pregnancy rate, miscarriage rate and clinical live birth rate. In stratified analysis, the variables of G3’ were not significantly different. In G4’, duration of HMG (8.74±2.31 vs. 7.90±2.56, P﹤0.05) was significantly different, which means for non-first cycle POR patients who reached or were older than 35 years old, GH addition may not be beneficial, nevertheless, the number of oocytes retrieved(8.74±2.31 vs. 7.90±2.56, P﹤0.05), clinical pregnancy rate(22.97% vs. 8.45%, P﹤0.05), and clinical live birth rate(14.86% vs. 4.23%, P﹤0.05) were significantly different between GH and control groups, all these results indicate that GH may remarkably improve the clinical outcomes of the non-first cycle POR patients who reached or were older than 35 years old.
Linear regression and logistic regression analysis were also performed in non-first cycles (table 6). In group all’, the number of oocytes retrieved(β=0.59, 95%CI[0.10, 1.08], P﹤0.05), the number of 2PN(β=0.51, 95%CI[0.11, 0.91], P﹤0.05), live birth rate(β=2.08, 95%CI[1.02, 4.25], P﹤0.05) were significantly improved in GH group. In G3’, the cycle characteristics and clinical outcomes were comparable between GH and control group. In group G4’, the number of oocytes retrieved(β=0.91, 95%CI[0.28, 1.53], P﹤0.05), the number of 2PN(β=0.56, 95%CI[0.05, 1.07], P﹤0.05), the number of transferrable embryos(β=0.42, 95%CI[0.00, 0.84], P﹤0.05) , clinical pregnancy rate(OR=3.06 95%CI[1.02, 9.17], P﹤0.05) and live birth rate(OR=5.26, 95%CI[1.13, 24.49], P﹤0.05) were significantly improved in GH group. The above results show that for POR patients who were failed in previous cycles, GH may increase the number of oocytes retrieved, 2PNs and live birth rate, for younger ones, GH may have no significant effects on the clinical outcomes, for older ones, GH obviously increase the number of oocytes retrieved, 2PNs, transferrable embryos and clinical pregnancy rate and live birth rate.
Table 4 Basal characteristics of non-first cycle patients.
|
All
|
<35
|
≥35
|
GH(n=122)
|
control(n=152)
|
P
|
GH(n=48)
|
control(n=81)
|
P
|
GH(n=74)
|
control(n=71)
|
P
|
Age(years)
|
35.35±5.78
|
35.01±5.46
|
0.619
|
29.17±2.82
|
30.79±2.77
|
0.002*
|
39.36±2.95
|
39.83±3.35
|
0.375
|
BMI(kg/m2)
|
23.24±2.97
|
23.00±3.01
|
0.513
|
22.79±2.99
|
22.83±2.28
|
0.944
|
23.53±2.95
|
23.20±2.67
|
0.477
|
Duration of infertilty(years)
|
4.61±3.78
|
5.34±3.86
|
0.117
|
4.40±2.30
|
4.85±2.72
|
0.339
|
4.74±4.50
|
5.90±4.80
|
0.138
|
AMH(ng/ml)
|
0.68±0.30
|
0.64±0.28
|
0.269
|
0.79±0.25
|
0.66±0.30
|
0.010*
|
0.60±0.30
|
0.61±0.26
|
0.795
|
FSH(IU/L)
|
10.20±3.96
|
9.87±3.88
|
0.487
|
9.20±3.14
|
9.25±3.40
|
0.948
|
10.84±4.32
|
10.57±3.65
|
0.686
|
LH(IU/L)
|
3.78±1.66
|
3.84±1.86
|
0.781
|
3.78±1.65
|
3.66±2.14
|
0.735
|
3.78±1.68
|
4.05±1.47
|
0.34
|
E2(pg/ml)
|
43.42±17.00
|
43.73±20.59
|
0.892
|
48.64±18.70
|
44.61±22.33
|
0.296
|
40.04±14.98
|
42.75±18.51
|
0.334
|
AFC(n)
|
4.51±2.14
|
4.68±2.22
|
0.508
|
5.08±2.26
|
4.94±2.17
|
0.718
|
4.14±1.99
|
4.39±2.25
|
0.462
|
Table 5 Cycle characteristics of non-first cycle patients.
|
All’
|
G3’
|
G4’
|
GH(n=122)
|
control(n=152)
|
P
|
GH(n=48)
|
control(n=81)
|
P
|
GH(n=74)
|
control(n=71)
|
P
|
Duration of HMG(days)
|
8.48±2.19
|
8.30±2.34
|
0.517
|
8.06±1.96
|
8.64±2.08
|
0.12
|
8.74±2.31
|
7.90±2.56
|
0.039*
|
Dosage of HMG( IU)
|
1730.53±655.41
|
1669.24±662.13
|
0.445
|
1625.00±524.96
|
1727.78±614.52
|
0.335
|
1798.99±722.85
|
1602.47±711.09
|
0.101
|
Oocytes retrieved(n)
|
3.16±2.71
|
2.66±2.11
|
0.093
|
3.69±2.80
|
3.28±2.35
|
0.382
|
2.81±2.61
|
1.96±1.53
|
0.018*
|
2PN(n)
|
2.22±2.03
|
1.82±1.70
|
0.073
|
2.67±2.18
|
2.16±1.90
|
0.169
|
1.93±1.88
|
1.42±1.34
|
0.063
|
embryos(n)
|
2.15±2.04
|
1.88±1.87
|
0.262
|
2.60±2.27
|
2.30±2.16
|
0.444
|
1.85±1.83
|
1.41±1.34
|
0.099
|
Transferrable embryos(n)
|
1.47±1.62
|
1.26±1.28
|
0.236
|
1.55±1.78
|
1.47±1.39
|
0.767
|
1.42±1.52
|
1.03±1.10
|
0.079
|
Good-quality embryos(n)
|
1.14±1.57
|
0.96±1.00
|
0.253
|
1.27±1.81
|
1.06±1.03
|
0.403
|
1.05±1.39
|
0.85±0.97
|
0.298
|
Clinical pregnancy(%)
|
33(27.05%)
|
29(19.08%)
|
0.117
|
16(33.33%)
|
23(28.40%)
|
0.555
|
17(22.97%)
|
6(8.45%)
|
0.017*
|
Miscarriage(%)
|
6(4.92%)
|
8(5.26%)
|
0.897
|
0(0.00%)
|
5(6.17%)
|
0.079
|
6(8.11%)
|
3(4.23%)
|
0.333
|
Live birth(%)
|
26(21.31%)
|
20(13.16%)
|
0.073
|
15(31.25%)
|
17(20.99%)
|
0.192
|
11(14.86%)
|
3(4.23%)
|
0.030*
|
Table 6 Linear regression and logistic regression analysis of non-first cycle patients.
group
|
|
β/OR
|
95%CI
|
P
|
All’
|
Duration of HMG
|
0.08
|
(-0.46-0.61)
|
0.782
|
Dosage of HMG
|
27.86
|
(-119.36-175.07)
|
0.71
|
Oocytes retrieved
|
0.59
|
(0.1-1.08)
|
0.018*
|
2PN
|
0.51
|
(0.11-0.91)
|
0.012*
|
embryos
|
0.35
|
(-0.09-0.78)
|
0.118
|
Transferrable embryos
|
0.27
|
(-0.06-0.6)
|
0.106
|
Good-quality embryos
|
0.21
|
(-0.09-0.51)
|
0.173
|
Clinical pregnancy
|
1.79
|
(0.97-3.31)
|
0.062
|
Miscarriage
|
0.84
|
(0.27-2.61)
|
0.756
|
Live birth
|
2.08
|
(1.02-4.25)
|
0.044*
|
G3’
|
Duration of HMG
|
-0.71
|
(-1.49-0.07)
|
0.073
|
Dosage of HMG
|
-113.42
|
(-322.93-96.1)
|
0.286
|
Oocytes retrieved
|
0.31
|
(-0.52-1.13)
|
0.462
|
2PN
|
0.6
|
(-0.06-1.26)
|
0.076
|
embryos
|
0.42
|
(-0.35-1.19)
|
0.281
|
Transferrable embryos
|
0.09
|
(-0.48-0.66)
|
0.751
|
Good-quality embryos
|
0.18
|
(-0.34-0.7)
|
0.489
|
Clinical pregnancy
|
1.5
|
(0.61-3.71)
|
0.381
|
Miscarriage
|
/
|
/
|
/
|
Live birth
|
1.69
|
(0.65-4.35)
|
0.28
|
G4’
|
Duration of HMG
|
0.74
|
(-0.05-1.53)
|
0.066
|
Dosage of HMG
|
150.1
|
(-71.12-371.32)
|
0.182
|
Oocytes retrieved
|
0.91
|
(0.28-1.53)
|
0.005*
|
2PN
|
0.56
|
(0.05-1.07)
|
0.033*
|
embryos
|
0.48
|
(-0.03-0.99)
|
0.065
|
Transferrable embryos
|
0.42
|
(0-0.84)
|
0.049*
|
Good-quality embryos
|
0.24
|
(-0.15-0.63)
|
0.235
|
Clinical pregnancy
|
3.06
|
(1.02-9.17)
|
0.046*
|
Miscarriage
|
1.47
|
(0.31-6.98)
|
0.625
|
Live birth
|
5.26
|
(1.13-24.49)
|
0.034*
|