Baseline characteristics of the three groups
No significant differences in the mean age, body mass index (BMI), baseline FSH level, AFC, and year of infertility were observed among groups A, B, and C (P > 0.05). The hormone levels of the three groups on the day of hCG trigger were compared, and the results revealed no significant difference in the mean progesterone levels (P > 0.05); however, the mean E2 and LH levels, ratio of premature LH peak (> 10 mIU/ml), and ratio of high progesterone levels (> 1.0 ng/ml) showed significant differences (P < 0.05). Significant differences in the time interval between oocyte retrieval and hCG trigger, number of follicles ≥ 11 mm in diameter, and dosage regimen of Gn were observed among the three groups in comparison with those in group C (P < 0.05) (Table 1).
Table 1
Comparison of general basic data among groups A, B, and C.
Characteristics | Group A (n = 585) | Group B (n = 235) | Group C (n = 158) | P-value |
Age(year) | 37.77 ± 5.10 | 37.79 ± 5.21 | 38.25 ± 4.96 | 0.563 |
Infertility year (year) | 4.56 ± 4.36 | 4.17 ± 3.79 | 4.14 ± 2.04 | 0.294 |
BMI (Kg/m2) | 22.07 ± 2.85 | 21.88 ± 2.85 | 21.82 ± 2.85 | 0.518 |
Baseline FSH (IU/L) | 10.25 ± 5.60 | 10.20 ± 5.17 | 10.43 ± 4.95 | 0.915 |
AFC count(n) | 3.92 ± 2.01 | 4.15 ± 1.94 | 3.87 ± 2.23 | 0.287 |
The total dosages of Gn (IU) | 1991.62 ± 1115.07 | 1990.48 ± 1014.74 | 1560.36 ± 1162.72 | 0.000 |
The total days of Gn (days) | 7.95 ± 3.15 | 7.99 ± 3.06 | 6.53 ± 4.11 | 0.000 |
Number of ≥ 11 mm follicles (n) | 3(2,4) | 3(1,6) | 4(2,7) | 0.000 |
E2 levels on the day of hCG (ng/ml) | 1026.5(615.85,1636.25) | 1005(632.5,1773.50) | 800(439.9,1582) | 0.047 |
LH levels on the day of hCG (IU/l) | 3.84(2.39,5.66) | 4.27(2.47,7.81) | 8.08(3.78,14.29) | 0.000 |
P levels on the day of hCG (ng/ml) | 0.54(0.33,0.8) | 0.60(0.32,0.8) | 0.56(0.31,0.96) | 0.352 |
The ratio of premature LH peak (%) | 6.2(36/585) | 17(40/235) | 39.2(62/158) | 0.000 |
The ratio of progesterone levels > 1.0ng/ml (%) | 14(82/585) | 21.3(50/235) | 22.8(36/158) | 0.006 |
The time interval (h) | 35.40 ± 3.15 | 34.92 ± 4.21 | 33.11 ± 7.56 | 0.000 |
Gn: gonadotropin; The time interval (h): the time interval between the hCG trigger and oocyte retrieval. |
Laboratory Data Of The Three Groups
The number of oocytes retrieved, OCCs rate, unexpected ovulation rate, rate of non-retrieved oocytes, mature oocyte rate, fertilization rate, and rate of obtaining high-quality embryos showed significant differences among the three groups (P < 0.05). With increasing △E2%, the unexpected ovulation rate of group C (8.9 %) was higher than that of group A (0.9%) and B (2.6 %) (P < 0.05, Table 2).
Table 2
Comparison of laboratory data of the three groups
Factors | Group A (n = 585) | Group B (n = 235) | Group C (n = 158) | P-value |
The number of oocytes retrieved (n) | 3(2,6) | 3(2,5) | 2(1,3) | 0.000 |
The OCCs rate(%) | 84.32 ± 24.30 | 82.78 ± 27.10 | 71.89 ± 37.55 | 0.000 |
The premature ovulation rate (%) | 0.9(5/585) | 2.6(6/235 | 8.9(14/158) | 0.000 |
The oocytes non-retrieved rate (%) | 3.6(21/585) | 5.5(13/235) | 16.5(26/158) | 0.000 |
The mature oocyte rate (%) | 85.24 ± 26.34 | 83.37 ± 29.69 | 72.34 ± 40.66 | 0.000 |
The fertilization rate (%) | 66.35 ± 32.87 | 67.11 ± 34.79 | 56.21 ± 42.03 | 0.003 |
The utilizable embryos rate (%) | 72.99 ± 38.88 | 72.79 ± 39.84 | 55.78 ± 46.60 | 0.000 |
The high-quality embryo rate (%) | 63.34 ± 40.43 | 63.02 ± 40.96 | 45.11 ± 44.64 | 0.000 |
Logistic regression analysis of relation between △E2% and unexpected ovulation
Group A was considered the reference group. The likelihood ratio of unexpected ovulation rate in groups B and C was 3.36 (95% CI: 0.75–5.13) and 18.86 % (95% CI, 5.35–66.51), respectively, in comparison with that in group A. After adjusting for age; basal FSH level; AFC; gonadotropin dosage regimen; and levels of E2, LH, and progesterone on the day of hCG trigger, and the time interval between hCG trigger and oocyte retrieval, the likelihood ratio of unexpected ovulation rate in groups B and C was 2.96 (95% CI: 0.64–13.70) and 11.74% (95% CI: 3.09–44.62), respectively. The test for trend was statistically significant before and after correction (P < 0.05).
Moreover, it was concluded that the risk of unexpected ovulation increased by 2.27 times for one standard deviation (SD) (approximately 10%) increase in △E2% (95 % CI: 1.76–2.94). After adjusting relevant confounders, the risk of unexpected ovulation increased by 2.22 times (95% CI: 1.72–2.87) (Table 3).
Table 3
Logistic regression analysis of relation between △E2% and unexpected ovulation
Factors | Odds ratio (95% CI) | Odds ratio-adjusted (95% CI) |
Group A(△E2%<10%) | Ref | Ref |
Group B(10%>△E2%>20%) | 3.36(0.75–15.13) | 2.96(0.64–13.70) |
Group C(△E2%༞20%) | 18.86(5.35–66.51) | 11.74(3.09–44.62) |
P for trend | 0.000 | 0.000 |
Per 10% (1 SD) decrement | 2.27(1.76–2.94) | 2.22(1.72–2.87) |
ROC curve analysis of predictive value of △E2% for unexpected ovulation
To assess the predictive value of △E2% for unexpected ovulation, ROC curves were generated. When we combined premature LH peak (> 10 mIU/ml) or high progesterone level (> 1.0 ng/ml) on the day of hCG trigger, the AUC was 0.849 (95% CI: 0.764–0.934, P < 0.05), and the maximum Youden Index was 0.610, with a cut-off of 0.260 (Fig. 1). However, when we considered only △E2%, the AUC was 0.738 (95% CI: 0.562–0.914, P < 0.05), and the maximum Youden Index was 0.380, with a cut-off of 0.072 (Fig. 2). Therefore, the results suggest that the △E2% > 26% in cycles with premature LH peak and high progesterone levels on the day of hCG trigger is a valuable predictor of unexpected ovulation.
Clinical Data Of Subgroups A1,b1, And C1
A total of 295 cases of fresh embryo transfer were performed in the study data, comprising 189 cases of fresh embryo transfer cycle in group A (marked as group A1), 79 cases in group B (marked as group B1), and 27 cases in group C (marked as group C1). Comparison of the baseline characteristics and clinical outcomes of the three subgroups showed no significant difference in mean age, years of infertility, BMI, baseline FSH level, AFC counts, and the total dosages of gonadotropin (P > 0.05). The three subgroups were balanced and comparable. There was no significant difference in the rates of embryo implantation, clinical pregnancy, live birth in fresh embryo transfer cycle, and early abortion among the three subgroups (P > 0.05) (Table 4).
Table 4
Comparison of baseline characteristics and clinical outcomes among subgroups A1, B1, and C1.
Factors | Group A1 (n = 189) | Group B1 (n = 79) | Group C1 (n = 27) | P-value |
Age(year) | 36.73 ± 5.06 | 35.65 ± 5.26 | 36.85 ± 5.05 | 0.262 |
Infertility year (year) | 4.40 ± 3.90 | 3.74 ± 2.97 | 4.30 ± 2.51 | 0.389 |
BMI (Kg/m2) | 21.83 ± 2.60 | 21.10 ± 2.52 | 21.84 ± 3.01 | 0.107 |
Baseline FSH (IU/L) | 8.76 ± 3.70 | 8.79 ± 3.34 | 8.75 ± 3.58 | 0.959 |
AFC count(n) | 4.49 ± 1.88 | 4.77 ± 1.98 | 4.26 ± 2.18 | 0.396 |
The total dosages of Gn (IU) | 2621.30 ± 877.70 | 2572.78 ± 715.20 | 2217.11 ± 891.91 | 0.088 |
Endometrium thickness on day of ET (mm) | 9.83 ± 2.10 | 9.72 ± 2.10 | 9.38 ± 1.65 | 0.571 |
Embryo transfer number (n) | 1.83 ± 0.42 | 1.80 ± 0.46 | 1.82 ± 0.42 | 0.783 |
Embryo implantation rate (%) | 27.8(97/349) | 33.1(47/142) | 26.0(13/50) | 0.444 |
Clinical Pregnancy rate (%) | 42.3(80/189) | 43.0(34/79) | 37.0(10/27) | 0.854 |
The early abortion rate (%) | 21.3(17/80) | 17.6(6/34) | 30.0(3/10) | 0.697 |
Live birth rate (%) | 29.1(55/189) | 32.9(26/79) | 18.5(5/27) | 0.364 |
ET: embryo transfer. |