Baseline characteristics
The patients’ baseline characteristics and clinical features are shown in Table 1. There were no significant differences between the two groups with regard to age, BMI, duration of infertility, basal serum follicle stimulating hormone (FSH) levels, basal luteinizing hormone (LH) levels, basal E2 levels, or type of infertility. In addition, their characteristics related to OHSS risk factors, including ovarian antral follicle count (AFC) and anti-Müllerian hormone (AMH) levels were also similar between in the study or control groups (Table 1).
Table 1 Baseline characteristics and clinical features of patients in two groups
Variables
|
Bromocriptine (n=52)
|
I.V HES (n=52)
|
P-value
|
Age (y)
|
31.31±3.85
|
29.68±3.06
|
0.093
|
BMI (kg/m2 )
|
22.36±2.33
|
24.07±4.15
|
0.239
|
Duration of infertility (y)
|
2.33±1.15
|
3.14±2.03
|
0.216
|
Basal FSH (mIU/ml)
|
6.20±1.72
|
6.00±1.18
|
0.638
|
Basal LH (mIU/ml)
|
5.01±4.05
|
5.79±2.35
|
0.412
|
Basal E2 (pg/ml)
|
48.49±14.71
|
44.97±14.11
|
0.403
|
Basal AMH (ng/ml)
|
8.38±5.37
|
9.52±4.62
|
0.125
|
antral follicle count (AFC)
|
18.09±4.25
|
19.10±3.30
|
0.150
|
Type of infertility
|
|
|
|
Primary infertility, n(%)
|
27 (51.92)
|
29 (55.77)
|
0.187
|
Secondary infertility, n(%)
|
25 (48.08)
|
23 (44.23)
|
|
Note: Values represent means ± standard deviation (SD) or number (percentage)
Ovarian stimulation outcomes
No significant differences were found between the rectal bromocriptine administration or I.V. HES groups in terms of their duration of ovarian stimulation in days (P>0.05), total amount of gonadotropin (Gn) dose (P>0.05), and endometrial thickness on the day of trigger (P>0.05). The subjects’ characteristics were also similar between groups in relation to OHSS-associated risk factors including E2 levels on the day of trigger, on the day of ovum pick-up (OPU), and on the 5th day after oocyte retrieval, as well as in the number of retrieved oocytes (Table 2).
Table 2 Ovarian stimulation outcomes in two groups
Variable
|
Bromocriptine (n=52)
|
I.V HES (n=52)
|
P-value
|
Stimulation length (d)
|
10.27±1.74
|
9.61±1.99
|
0.346
|
Gn dose (IU)
|
2059.09±304.40
|
2057.14±552.45
|
0.991
|
E2 on the day of trigger (pg/ml)
|
5811.88±1940.20
|
6083.99±2159.79
|
0.245
|
LH on the day of trigger (mIU/ml)
|
1.35±1.11
|
1.83±2.21
|
0.321
|
P on the day of trigger (ng/ml)
|
1.11±0.42
|
1.25±0.63
|
0.165
|
E2 on Day 0 (pg/ml)
|
3170.38±1157.99
|
3538.36±1438.60
|
0.329
|
E2 on Day 5 (pg/ml)
|
3209.22±1724.45
|
2869.71±2001.64
|
0.452
|
Endometrial thickness on day of trigger (mm)
|
10.80±2.22
|
10.67±2.21
|
0.873
|
No. of retrieved oocytes (n)
|
23.89±4.01
|
24.75±3.06
|
0.061
|
Note: Values represent means ± standard deviation (SD)
Day 0: on the day of ovum pick-up (OPU)
Day 5: on the 5th day after oocyte retrieval
OHSS Outcomes
o significant differences were observed in the incidence of mild or moderate OHSS between the bromocriptine and HES groups. Moderate OHSS was observed in 4 patients in the bromocriptine group, while 3 cases occurred in the HES group (7.69% vs 5.77%), with no significant differences in the two groups. These cases were all categorized as “early OHSS”, and no severe OHSS or late OHSS were observed in either the study or control groups (Table 3).
Table 3 Incidence of OHSS in patients given bromocriptine or HES
|
Bromocriptine (n=52)
|
I.V HES (n=52)
|
P-value
|
Mild OHSS, n(%)
|
7 (13.46)
|
8 (15.38)
|
0.78
|
Moderate OHSS, n(%)
|
4 (7.69)
|
3 (5.77)
|
0.69
|
Overall OHSS, n(%)
|
11 (21.15)
|
11 (21.15)
|
1.00
|
Early OHSS, n(%)
|
11 (21.15)
|
11 (21.15)
|
1.00
|
Note: Data are expressed as number (percentage)
There were no significant differences found between the two groups in their baseline HCT, WBC, and PLT counts (i.e., before ovarian stimulation). However, on the 5th day after oocyte retrieval, WBC counts were significantly higher in both groups compared with their baseline WBC (P <0.05). Furthermore, WBC count and HCT were both significantly higher in the bromocriptine group compared to the HES group (P <0.05) on the 5th day after oocyte retrieval (Table 4).
Table 4 Blood-related parameters before ovarian stimulation and on the 5th day after oocyte retrieval
Variable
|
Bromocriptine (n=52)
|
I.V. HES (n=52)
|
HCT (%)
|
|
|
Baseline
|
40.23±2.42
|
40.00±2.35
|
On Day 5
|
41.43±1.93*
|
39.52±3.29
|
WBC count(×109/L)
|
|
|
Baseline
|
7.28±2.82
|
6.41±1.25
|
On Day 5
|
13.95±4.51*#
|
10.83±2.88#
|
PLT count (×109/L)
|
|
|
Baseline
|
260.75±61.97
|
282.26±54.01
|
On Day 5
|
302.70±74.42
|
297.76±51.11
|
Note: Values represent means ± standard deviation (SD)
* Compared to the I.V. HES group at the same period; # Compared to the same group at baseline before ovarian
Haematocrit: HCT; White blood cell: WBC; platelet: PLT
Baseline: before ovarian stimulation
On Day 5: on the 5th day after oocyte retrieval
There were no statistically significant differences in coagulation and fibrinolytic parameters before ovarian stimulation between patients who received bromocriptine versus HES; only the activated partial thromboplastin time (APTT) was lower in the bromocriptine group than in the HES group on the 5th day after oocyte retrieval (P< 0.05). FIB, TT and D-D were significantly higher in both groups compared with their baseline levels (all P <0.05) (Table 5).
Table 5 Coagulation and fibrinolytic parameters at baseline and on the 5th day after oocyte retrieval
Variables
|
Bromocriptine (n=52)
|
I.V HES (n=52)
|
FIB (g/L)
|
|
|
Baseline
|
2.82±0.55
|
2.83±0.58
|
On Day 5
|
3.79±0.69#
|
4.02±1.09#
|
PT (s)
|
|
|
Baseline
|
11.17±0.70
|
11.06±0.46
|
On Day 5
|
10.95±0.56
|
10.95±0.45
|
PA (%)
|
|
|
Baseline
|
112.48±17.46
|
116.39±11.36
|
On Day 5
|
119.74±12.70
|
119.09±9.53
|
TT (s)
|
|
|
Baseline
|
17.41±0.71
|
17.76±1.09
|
On Day 5
|
16.25±1.14#
|
15.86±0.80#
|
APTT (s)
|
|
|
Baseline
|
26.28±3.49
|
26.53±2.68
|
On Day 5
|
22.69±2.55*#
|
25.43±2.42
|
D-D (mg/L)
|
|
|
Baseline
|
0.27±0.22
|
0.25±0.11
|
On Day 5
|
1.91±1.46#
|
1.83±1.29#
|
Note: Values represent means ± standard deviation (SD)
* Compared to the I.V. HES group at the same period; # Compared to the same group at baseline before ovarian stimulation.
FIB: fibrinogen; PT: prothrombin time ; PA: plasminogen activator; TT: thrombin time; APTT: activated partial thromboplastin time; D-D: D-dimer.
Baseline: before ovarian stimulation
On Day 5: on the 5th day after oocyte retrieval
In assays for liver and kidney function, we found no significant difference between the two groups, either at baseline prior to ovarian stimulation or on the 5th day after oocyte retrieval (P >0.05). Both groups showed significantly higher transaminase activities, including ALT and AST, on the 5th day after oocyte retrieval compared with baseline (P <0.05) (Table 6).
Table 6 Liver and renal function before ovarian stimulation and on the 5th day after oocyte retrieval in the two groups
Variable
|
Bromocriptine (n=52)
|
I.V HES (n=52)
|
ALT (U/L)
|
|
|
Baseline
|
13.74±6.24
|
15.70±13.50
|
On Day 5
|
23.06±16.28#
|
25.87±14.31#
|
AST(U/L)
|
|
|
Baseline
|
15.89±3.92
|
16.14±4.97
|
On Day 5
|
23.43±14.40#
|
22.58±10.81#
|
GGT(U/L)
|
|
|
Baseline
|
16.38±7.73
|
17.93±16.95
|
On Day 5
|
23.29±22.30
|
25.00±24.31
|
BUN (mmol/L)
|
|
|
Baseline
|
4.14±0.89
|
3.88±0.91
|
On Day 5
|
4.39±0.82
|
4.14±0.78
|
UA (μmol/L)
|
|
|
Baseline
|
298.83±75.93
|
282.66±56.80
|
On Day 5
|
265.92±63.08
|
299.79±95.74
|
CRE (μmol/L)
|
|
|
Baseline
|
53.85±7.49
|
53.75±8.19
|
On Day 5
|
57.09±6.30
|
56.10±6.93
|
eGFR (ml/min/1.73m2)
|
|
|
Baseline
|
126.65±21.85
|
128.08±22.74
|
On Day 5
|
116.38±14.98
|
120.69±19.53
|
Note: Values represent means ± standard deviation (SD)
# Compared to the same group at baseline before ovarian
ALT: alanine aminotransferase; AST: aspartate aminotransferase; GGT: glutamyl transpeptidase; BUN: blood urea nitrogen; UA: uric acid; CRE: creatinine; eGFR: estimated glomerular filtration rate.
Baseline: before ovarian stimulation
On Day 5: on the 5th day after oocyte retrieval
In addition, the medication was well-tolerated by all patients in the study group, with no obvious side effects recorded in either the bromocriptine or HES groups.