Table 3.
Cumulative Live Births and Pregnancy Outcomes (Intention-to-Treat Analysis)
| Outcomes, No./total (%) | Blastocyst-stage embryo transfer group (n = 497) | Cleavage-stage embryo transfer group (n = 495) | Absolute difference (95% CI)a | Relative risk (95% CI) | P valueb |
|---|---|---|---|---|---|
| Primary outcome | |||||
| Cumulative live birthsc | 372 (74.8) | 328 (66.3) | 8.6 (2.9 to 14.2) | 1.13 (1.04 to 1.22) | 0.003 |
| Singleton live births | 363 (73.0) | 324 (65.5) | 7.6 (1.9 to 13.3) | 1.12 (1.03 to 1.21) | 0.010 |
| All twin live births | 9 (1.8) | 4 (0.8) | 1.0 (−0.4 to 2.4) | 2.24 (0.69 to 7.23) | 0.17 |
| Monozygotic twin live births | 7 (1.4) | 2 (0.4) | 1.0 (−0.2 to 2.2) | 3.49 (0.73 to 16.70) | 0.18 |
| Secondary outcomes | |||||
| Cumulative biochemical pregnanciesd | 430 (86.5) | 399 (80.6) | 5.9 (1.3 to 10.5) | 1.07 (1.02 to 1.13) | 0.01 |
| Cumulative clinical pregnanciese | 416 (83.7) | 378 (76.4) | 7.3 (2.4 to 12.3) | 1.10 (1.03 to 1.17) | 0.004 |
| Cumulative ongoing pregnanciesf | 385 (77.5) | 336 (67.9) | 9.6 (4.1 to 15.1) | 1.14 (1.06 to 1.23) | 0.00070 |
| Cumulative pregnancy loss | |||||
| Biochemical pregnancy loss | 37 (7.4) | 36 (7.3) | 0.2 (−3.1 to 3.4) | 1.02 (0.66 to 1.59) | 0.92 |
| Clinical pregnancy loss | 54 (10.9) | 54 (10.9) | −0.0 (−3.9 to 3.8) | 1.00 (0.70 to 1.42) | 0.98 |
| Miscarriage <12 weeks gestation | 43 (8.7) | 49 (9.9) | −1.2 (−4.9 to 2.4) | 0.87 (0.59 to 1.29) | 0.50 |
| Miscarriage 12-24 weeks gestation | 11 (2.2) | 5 (1.0) | 1.2 (−0.4 to 2.8) | 2.19 (0.77 to 6.26) | 0.13 |
| Ectopic pregnancy | 7 (1.4) | 11 (2.2) | −0.8 (−2.5 to 0.8) | 0.63 (0.25 to 1.62) | 0.34 |
| Live birth after first embryo transferg | 256/486 (52.7) | 200/491 (40.7) | 11.9 (5.7 to 18.2) | 1.29 (1.13 to 1.48) | 0.00018 |
| Live birth after second embryo transfer | 89/189 (47.1) | 85/261 (32.6) | 14.5 (5.4 to 23.6) | 1.45 (1.15 to 1.82) | 0.002 |
| Live birth after third embryo transfer | 21/52 (40.4) | 36/123 (29.3) | 11.1 (−4.5 to 26.7) | 1.38 (0.90 to 2.12) | 0.15 |
| Live birth after natural conception | 6 (1.2) | 7 (1.4) | −0.2 (−1.6 to 1.2) | 0.85 (0.29 to 2.52) | 0.78 |
| Median time to livebirth since randomization, daysh | 344 (334−353)i | 373 (353 − 416)i | −31.3 (−32.2 to −30.4) | 1.26 (1.09 to 1.47)j | 0.002k |
| No. of unused frozen embryos, mean (SD) | 4.1 (3.3) | 5.9 (4.0) | −1.8 (−2.3 to −1.3) | - | 3.37e-14 |
| No. of unused frozen embryos in women with a live birth, mean (SD) | 4.7 (3.3) | 6.4 (3.8) | −1.7 (−2.2 to −1.2) | - | 7.15e-10 |
| No. of unused frozen embryos in women without a live birth, mean (SD) | 2.2 (2.6) | 4.9 (4.2) | −2.7 (−3.4 to −1.9) | - | 2.03e-09 |
| No. of women without a frozen embryo | 71 (14.3) | 23 (4.6) | 9.6 (6.0 to 13.2) | 3.07 (1.95 to 4.84) | 2.18e-07 |
| No. of women without a frozen embryo without a livebirth | 46 (9.3) | 22 (4.4) | 4.8 (1.7 to 7.9) | 2.08 (1.27 to 3.41) | 0.003 |
| No. of women without a frozen embryo with a livebirth | 25 (5.0) | 1 (0.2) | 4.8 (2.9 to 6.8) | 24.90 (3.39 to183.05) | 1.94e-06 |
SD standard deviation.
aAbsolute differences in percentages are indicated in percentage points, and absolute differences in other values are indicated in units of that value.
bAll P values are for superiority, two-sided. No adjustments were made for multiple comparison. Two-sample t-test was used for continuous variable; Chi-square test was used for categorical data.
cCumulative live births were calculated from up to the first 3 embryo transfers in 1 year after randomization (with a 3-months extension for those affected by Covid-19) from one oocyte retrieval cycle. Live birth was defined as delivery of any neonate ≥24 weeks gestation that had a heartbeat and was breathing. P = 5.60e-11 for non-inferiority (with margin = −0.1, α = 0.025, one-sided).
dBiochemical pregnancy was defined as serum human chorionic gonadotropin ≥25 IU/L 14 days after embryo transfer.
eClinical pregnancy was defined as detection of intrauterine gestation sacs at 30–35 days after embryo transfer. One woman in the cleavage-stage group was lost to follow-up after confirmation of clinical pregnancy.
fOngoing pregnancy was defined as detection of a viable fetus with heartbeat at 12 weeks’ gestation. One woman in the cleavage-stage group was lost to follow-up after confirmation of an ongoing pregnancy.
gLivebirth after the first embryo transfers included 235 livebirths from 536 fresh embryo transfer and 221 livebirths from 441 first frozen embryo transfer (freeze-only strategy).
hThe length of time from randomization to 50% of the participants who achieved a livebirth.
i95% confidence interval for median time to live birth.
jHazard ratio (95% confidence interval).
klog-rank test.