Introduction
Materials and methods
Patients
Endometrial preparation before embryo transfer
Outcomes
Statistical analysis
Results
Baseline and cycle characteristics
Variable | GnRHa + HRT (N = 389) | HRT (N = 950) | NC (N = 74) | P value |
---|---|---|---|---|
Maternal age at oocyte retrieval, y | 31.0 (29.0, 35.0) | 31.0 (29.0, 35.0) | 32.0 (30.0, 35.0) | 0.2013 |
Body mass index, kg/m2 | 20.8 (19.4, 22.5) | 20.8 (19.5, 22.8) | 21.1 (19.6, 22.6) | 0.7423 |
Baseline FSH, mIU/mL | 7.8 (6.6, 9.6) | 7.8 (6.5, 9.0) | 7.9 (6.4, 9.8) | 0.6653 |
Antral follicle count (AFC) | 8.0 (5.0, 11.0) | 9.0 (6.0, 14.0) | 7.0 (4.0, 13.0) | <.0013* |
AMH level, ng/ml | 2.4 (1.4, 4.5) | 2.8 (1.7, 5.3) | 2.1 (1.2, 4.0) | <.0013* |
Duration of infertility, years | 2.0 (1.5, 4.0) | 3.0 (2.0, 4.0) | 3.0 (2.0, 5.0) | 0.0063* |
Infertility diagnosis | 0.9691 | |||
Primary infertility, n (%) | 257 (66.1%) | 629 (66.2%) | 50 (67.6%) | |
Secondary infertility, n (%) | 132 (33.9%) | 321 (33.8%) | 24 (32.4%) | |
Infertility etiology, n (%) | ||||
Male factor | 64 (16.5%) | 167 (17.6%) | 19 (25.7%) | 0.1611 |
Female factors | ||||
Tubal factor | 189 (48.6%) | 472 (49.7%) | 35 (47.3%) | 0.8811 |
Ovulatory | 3 (0.8%) | 42 (4.4%) | 1 (1.4%) | 0.0012* |
Diminished ovarian reserve | 115 (29.6%) | 218 (22.9%) | 19 (25.7%) | 0.0391* |
Uterine malformation | 105 (27.0%) | 187 (19.7%) | 21 (28.4%) | 0.0061* |
Unexplained/Other | 0 (0.0%) | 6 (0.6%) | 1 (1.4%) | 0.1152 |
Ovarian stimulation protocols, n (%) | <.0011* | |||
Long GnRH-a | 43 (11.1%) | 165 (17.4%) | 12 (16.2%) | |
GnRH-a ultra-long | 98 (25.2%) | 342 (36.0%) | 25 (33.8%) | |
GnRH antagonist | 146 (37.5%) | 198 (20.8%) | 16 (21.6%) | |
Other protocols | 102 (26.2%) | 245 (25.8%) | 21 (28.4%) | |
Duration of stimulation, days | 10.0 (9.0, 11.0) | 10.0 (9.0, 11.0) | 10.0 (9.0, 11.0) | 0.0183* |
Gonadotropin dose, IU | 2625.0 (2100.0, 3150.0) | 2475.0 (1912.5, 3000.0) | 2625.0 (2137.5, 3150.0) | 0.0113* |
No. of oocytes retrieved | 9.0 (5.0, 14.0) | 10.0 (6.0, 16.0) | 8.0 (5.0, 14.0) | 0.0033* |
No. of MII oocytes | 7.0 (4.0, 12.0) | 9.0 (5.0, 14.0) | 7.0 (4.0, 12.0) | 0.0013* |
Oocyte maturation rate | 0.9 (0.8, 1.0) | 0.9 (0.8, 1.0) | 0.9 (0.8, 1.0) | 0.4783 |
Fertilization, n (%) | 0.0701 | |||
IVF | 105 (27.0%) | 199 (20.9%) | 23 (31.1%) | |
ICSI | 266 (68.4%) | 698 (73.5%) | 48 (64.9%) | |
Rescue ICSI | 18 (4.6%) | 53 (5.6%) | 3 (4.1%) | |
The number of 2PN | 5.0 (3.0, 9.0) | 6.0 (4.0, 10.0) | 5.0 (3.0, 10.0) | 0.0123* |
Normal fertilization rate | 0.7 (0.5, 0.9) | 0.7 (0.5, 0.8) | 0.7 (0.5, 0.9) | 0.1873 |
Blastocyst formation rate | 0.8 (0.5, 1.0) | 0.7 (0.5, 0.9) | 0.7 (0.5, 1.0) | 0.0253* |
Maternal age at FET, y | 32.0 (29.0, 35.0) | 32.0 (29.0, 35.0) | 33.0 (31.0, 35.0) | 0.0633 |
Interval between FET and IVF/ICSI, days | 125.0 (85.0, 248.0) | 91.0 (60.0, 172.0) | 112.0 (63.0, 263.0) | <.0013* |
No. of embryos thawed | 0.2262 | |||
1 | 242 (62.2%) | 537 (56.5%) | 44 (59.5%) | |
2 | 143 (36.8%) | 393 (41.4%) | 28 (37.8%) | |
> = 3 | 4 (1.0%) | 20 (2.1%) | 2 (2.7%) | |
No. of surviving embryos | 0.1942 | |||
1 | 243 (62.5%) | 540 (56.8%) | 44 (59.5%) | |
2 | 143 (36.8%) | 394 (41.5%) | 28 (37.8%) | |
3 | 3 (0.8%) | 16 (1.7%) | 2 (2.7%) | |
total no. of surviving embryos/no. of embryos thawed | 1.0 (1.0, 1.0) | 1.0 (1.0, 1.0) | 1.0 (1.0, 1.0) | 0.5283 |
No. of embryos transferred, n (%) | 0.3241 | |||
1 | 249 (64.0%) | 568 (59.8%) | 47 (63.5%) | |
2 | 140 (36.0%) | 382 (40.2%) | 27 (36.5%) | |
Type of embryo transferred, n (%) | 0.0291* | |||
Cleavage embryo | 142 (36.5%) | 296 (31.2%) | 32 (43.2%) | |
Blastocyst | 247 (63.5%) | 654 (68.8%) | 42 (56.8%) | |
Endometrial thickness, mm | 9.7 (8.8, 11.0) | 9.2 (8.4, 10.1) | 9.7 (8.8, 10.5) | <.0013* |
Luteal phase support, n (%) | <.0011* | |||
Intramuscular injection and oral administration | 11 (2.8%) | 179 (18.8%) | 10 (13.5%) | |
Vaginal gel administration and oral administration | 179 (46.0%) | 387 (40.7%) | 26 (35.1%) | |
Vaginal suppository administration and oral administration | 197 (50.6%) | 381 (40.1%) | 24 (32.4%) | |
Others | 2 (0.5%) | 3 (0.3%) | 14 (18.9%) | |
Live Birth, n (%) | 156 (40.1%) | 384 (40.4%) | 30 (40.5%) | 0.9941 |
Clinical Pregnancy, n (%) | 200 (51.4%) | 475 (50.0%) | 34 (45.9%) | 0.6771 |
Miscarriage, n (%) | 44 (11.3%) | 91 (9.6%) | 4 (5.4%) | 0.2812 |
Multiple pregnancy, n (%) | 37 (9.5%) | 108 (11.4%) | 4 (5.4%) | 0.2212 |
Biochemical Pregnancy, n (%) | 29 (7.5%) | 61 (6.4%) | 2 (2.7%) | 0.3212 |
Ectopic pregnancy, n (%) | 2 (0.5%) | 7 (0.7%) | 0 (0.0%) | >.9992 |
Clinical pregnancy outcomes
Variable | HRT vs. NC | GnRHa + HRT vs. NC | GnRHa + HRT vs. HRT | |||
---|---|---|---|---|---|---|
Crude OR (95% CI) | Adjusted OR (95% CI) | Crude OR (95% CI) | Adjusted OR (95% CI) | Crude OR (95% CI) | Adjusted OR (95% CI) | |
Live Birth a | 1.00 (0.61-1.61) | 0.83 (0.49-1.38) | 0.98 (0.59-1.63) | 0.86 (0.50-1.48) | 0.99 (0.78-1.26) | 1.04 (0.80-1.35) |
Clinical Pregnancy b | 1.18 (0.73-1.89) | 0.99 (0.60-1.64) | 1.24 (0.76-2.05) | 1.13 (0.67-1.93) | 1.06 (0.84-1.34) | 1.15 (0.89-1.48) |
Miscarriage c | 1.85 (0.66-5.20) | 1.80 (0.64-5.07) | 2.23 (0.78-6.41) | 2.22 (0.77-6.39) | 1.20 (0.82-1.76) | 1.23 (0.84-1.80) |
Multiple pregnancy d | 2.24 (0.80-6.27) | 1.91 (0.56-6.53) | 1.84 (0.64-5.32) | 2.24 (0.63-7.92) | 0.82 (0.55-1.21) | 1.17 (0.70-1.96) |
Biochemical Pregnancy e | 2.47 (0.59-10.30) | 2.31 (0.55-9.66) | 2.90 (0.68-12.41) | 2.80 (0.65-12.02) | 1.17 (0.74-1.86) | 1.21 (0.76-1.92) |
Singleton perinatal outcomes
Variable | GnRHa + HRT (N = 131) | HRT (N = 304) | NC (N = 30) | P value |
---|---|---|---|---|
Maternal age at oocyte retrieval, y | 30.0 (28.0, 33.0) | 30.0 (28.0, 33.0) | 32.0 (29.0, 33.0) | 0.3053 |
Body mass index, kg/m2 | 20.7 (19.2, 22.1) | 20.8 (19.5, 22.6) | 21.6 (19.7, 22.9) | 0.3403 |
Baseline FSH, mIU/mL | 7.7 (6.5, 8.9) | 7.5 (6.3, 8.8) | 7.7 (6.2, 8.5) | 0.7573 |
Antral follicle count (AFC) | 8.0 (5.0, 12.0) | 11.0 (7.0, 15.5) | 9.5 (6.0, 18.0) | <.0013* |
AMH level, ng/ml | 2.7 (1.4, 4.9) | 3.3 (2.1, 5.6) | 3.0 (1.6, 4.8) | 0.0143* |
Duration of infertility, years | 2.0 (1.5, 3.0) | 3.0 (1.5, 4.0) | 3.0 (2.0, 3.0) | 0.2843 |
Infertility diagnosis | 0.7471 | |||
Primary infertility, n (%) | 91 (69.5%) | 219 (72.0%) | 20 (66.7%) | |
Secondary infertility, n (%) | 40 (30.5%) | 85 (28.0%) | 10 (33.3%) | |
Infertility etiology, n (%) | ||||
Male factor | 21 (16.0%) | 50 (16.4%) | 5 (16.7%) | >.9992 |
Female factors | ||||
Tubal factor | 67 (51.1%) | 155 (51.0%) | 15 (50.0%) | 0.9941 |
Ovulatory | 1 (0.8%) | 12 (3.9%) | 1 (3.3%) | 0.1642 |
Diminished ovarian reserve | 29 (22.1%) | 43 (14.1%) | 3 (10.0%) | 0.0822 |
Uterine malformation | 30 (22.9%) | 44 (14.5%) | 9 (30.0%) | 0.0221* |
Unexplained/Other | 0 (0.0%) | 3 (1.0%) | 0 (0.0%) | 0.6382 |
Ovarian stimulation protocols, n (%) | 0.0051* | |||
Long GnRH-a | 21 (16.0%) | 66 (21.7%) | 8 (26.7%) | |
GnRH-a ultra-long | 34 (26.0%) | 124 (40.8%) | 13 (43.3%) | |
GnRH antagonist | 47 (35.9%) | 65 (21.4%) | 5 (16.7%) | |
Other protocols | 29 (22.1%) | 49 (16.1%) | 4 (13.3%) | |
Duration of stimulation, days | 10.0 (9.0, 11.0) | 10.0 (9.0, 11.0) | 10.0 (10.0, 12.0) | 0.0203* |
Gonadotropin dose, IU | 2625.0 (2025.0, 3165.0) | 2400.0 (1875.0, 3000.0) | 2550.0 (2100.0, 3075.0) | 0.1613 |
No. of oocytes retrieved | 9.0 (5.0, 14.0) | 12.0 (8.0, 17.0) | 11.0 (7.0, 16.0) | <.0013* |
No. of MII oocytes | 8.0 (4.0, 12.0) | 11.0 (7.0, 15.0) | 10.0 (6.0, 14.0) | <.0013* |
Oocyte maturation rate | 0.9 (0.8, 1.0) | 0.9 (0.8, 1.0) | 0.9 (0.9, 1.0) | 0.7453 |
Fertilization, n (%) | 0.3432 | |||
IVF | 35 (26.7%) | 62 (20.4%) | 5 (16.7%) | |
ICSI | 88 (67.2%) | 225 (74.0%) | 25 (83.3%) | |
Rescue ICSI | 8 (6.1%) | 17 (5.6%) | 0 (0.0%) | |
The number of 2PN | 6.0 (3.0, 8.0) | 7.0 (4.5, 10.5) | 8.0 (4.0, 11.0) | 0.0043* |
Normal fertilization rate | 0.7 (0.6, 0.9) | 0.7 (0.6, 0.8) | 0.7 (0.6, 0.9) | 0.1463 |
Blastocyst formation rate | 0.8 (0.6, 1.0) | 0.8 (0.5, 0.9) | 0.7 (0.5, 0.8) | 0.1173 |
Maternal age at FET, y | 31.0 (28.0, 34.0) | 31.0 (29.0, 33.0) | 32.0 (30.0, 33.0) | 0.3273 |
Interval between FET and IVF/ICSI, days | 131.0 (85.0, 229.0) | 90.5 (60.0, 166.0) | 80.5 (59.0, 220.0) | <.0013* |
No. of embryos thawed | 0.4802 | |||
1 | 19 (63.3%) | 187 (61.5%) | 89 (67.9%) | |
2 | 10 (33.3%) | 113 (37.2%) | 41 (32.1%) | |
> = 3 | 1 (3.3%) | 4 (1.3%) | 1 (0.8%) | |
No. of surviving embryos | 0.3142 | |||
1 | 19 (63.3%) | 188 (61.8%) | 89 (67.9%) | |
2 | 10 (33.3%) | 113 (37.2%) | 42 (32.1%) | |
> = 3 | 1 (3.3%) | 3 (1.0%) | 0 (0.0%) | |
total no. of surviving embryos/no. of embryos thawed | 1.0 (1.0, 1.0) | 1.0 (1.0, 1.0) | 1.0 (1.0, 1.0) | 0.8953 |
No. of embryos transferred, n (%) | 0.8161 | |||
1 | 89 (67.9%) | 198 (65.1%) | 19 (63.3%) | |
2 | 42 (32.1%) | 106 (34.9%) | 11 (36.7%) | |
Type of embryo transferred, n (%) | 0.0511 | |||
Cleavage embryo | 35 (26.7%) | 52 (17.1%) | 8 (26.7%) | |
Blastocyst | 96 (73.3%) | 252 (82.9%) | 22 (73.3%) | |
Endometrial thickness, mm | 10.1 (8.9, 11.3) | 9.3 (8.6, 10.3) | 9.3 (8.7, 10.4) | <.0013* |
Luteal phase support, n (%) | <.0011* | |||
Intramuscular injection and oral administration | 1 (0.8%) | 60 (19.7%) | 5 (16.7%) | |
Vaginal gel administration and oral administration | 64 (48.9%) | 128 (42.1%) | 9 (30.0%) | |
Vaginal suppository administration and oral administration | 66 (50.4%) | 115 (37.8%) | 9 (30.0%) | |
Others | 0 (0.0%) | 1 (0.3%) | 7 (23.3%) | |
Gestational age, wk | 38.9 (38.0, 39.4) | 39.0 (38.0, 39.6) | 38.6 (37.0, 39.0) | 0.0823 |
Birth weight, kg | 3.3 (3.0, 3.6) | 3.4 (3.1, 3.7) | 3.2 (2.7, 3.6) | 0.2373 |
Delivery mode, n (%) | 0.8481 | |||
Cesarean delivery | 114 (87.0%) | 260 (85.5%) | 25 (83.3%) | |
Natural labor | 17 (13.0%) | 44 (14.5%) | 5 (16.7%) | |
Gender, n (%) | 0.1601 | |||
Male | 81 (61.8%) | 159 (52.3%) | 15 (50.0%) | |
Female | 50 (38.2%) | 145 (47.7%) | 15 (50.0%) | |
Low birth weight < 2500 g | 9 (6.9%) | 19 (6.3%) | 2 (6.7%) | 0.9522 |
Macrosomia > 4000 g | 5 (3.8%) | 18 (5.9%) | 1 (3.3%) | 0.7262 |
Small for gestational age, n (%) | 10 (7.6%) | 17 (5.6%) | 4 (13.3%) | 0.1942 |
Large for gestational age, n (%) | 21 (16.0%) | 51 (16.8%) | 5 (16.7%) | 0.9791 |
Preterm birth < 37 wk., n (%) | 16 (12.2%) | 37 (12.2%) | 4 (13.3%) | 0.9452 |
Gestational diabetes mellitus, n (%) | 4 (3.1%) | 18 (5.9%) | 3 (10.0%) | 0.1852 |
Hypertensive disorders of pregnancy, n (%) | 125 (95.4%) | 291 (95.7%) | 29 (96.7%) | >.9992 |
Placenta previa, n (%) | 8 (6.1%) | 19 (6.3%) | 2 (6.7%) | >.9992 |
Fetal malformation, n (%) | 2 (1.5%) | 11 (3.6%) | 1 (3.3%) | 0.5102 |
Variable | HRT vs. NC | GnRHa + HRT vs. NC | GnRHa + HRT vs. HRT | |||
---|---|---|---|---|---|---|
Crude OR (95% CI) | Adjusted OR (95% CI) | Crude OR (95% CI) | Adjusted OR (95% CI) | Crude OR (95% CI) | Adjusted OR (95% CI) | |
Delivery mode | 1.18 (0.43-3.25) | 1.30 (0.47-3.61) | 1.34 (0.45-3.98) | 1.50 (0.50-4.49) | 1.13 (0.62-2.07) | 1.15 (0.63-2.11) |
Low birth weight < 2500 ga | 0.93 (0.21-4.22) | 2.12 (0.38-11.95) | 1.03 (0.21-5.05) | 1.45 (0.24-8.63) | 1.11 (0.49-2.51) | 0.68 (0.28-1.68) |
Macrosomia > 4000 gb | 1.83 (0.24-14.17) | 1.74 (0.22-13.77) | 1.15 (0.13-10.23) | 1.14 (0.13-10.33) | 0.63 (0.23-1.74) | 0.66 (0.24-1.82) |
Small for gestational agec, n (%) | 0.39 (0.12-1.23) | 0.42 (0.13-1.37) | 0.54 (0.16-1.85) | 0.48 (0.14-1.69) | 1.39 (0.62-3.12) | 1.14 (0.50-2.62) |
Large for gestational aged, n (%) | 1.01 (0.37-2.77) | 0.97 (0.35-2.69) | 0.95 (0.33-2.78) | 1.10 (0.37-3.26) | 0.94 (0.54-1.64) | 1.13 (0.64-2.01) |
Preterm birth < 37 wke, n (%) | 0.90 (0.30-2.73) | 0.68 (0.22-2.16) | 0.90 (0.28-2.93) | 0.68 (0.20-2.31) | 1.00 (0.54-1.88) | 0.99 (0.51-1.92) |
Gestational diabetes mellitusf, n (%) | 0.57 (0.16-2.05) | 0.67 (0.18-2.51) | 0.28 (0.06-1.34) | 0.27 (0.05-1.31) | 0.50 (0.17-1.51) | 0.40 (0.13-1.23) |
Hypertensive disorders of pregnancyg, n (%) | 1.30 (0.16-10.25) | 1.47 (0.17-12.78) | 1.39 (0.16-12.00) | 1.65 (0.17-15.87) | 1.07 (0.40-2.89) | 1.12 (0.39-3.22) |
Fetal malformationh, n (%) | 1.09 (0.14-8.74) | 0.96 (0.12-7.88) | 0.45 (0.04-5.13) | 0.41 (0.04-4.78) | 0.41 (0.09-1.89) | 0.43 (0.09-1.97) |