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Embryos reaching the morula stage before 70 hours post-ICSI present higher implantation rates
OBJECTIVE: The detection of multinucleation was compared with timelapse system and conventional control timing proposed by ESHRE consensus and its impact on pregnancy rate was researched. DESIGN: Retrospective study in an IVF Center. MATERIALS AND METHODS: A total of 686 transferred embryos from 511 IVF-ICSI patients were assessed based on the time-lapse monitoring system. All embryos were evaluated with EmbryoScope (EmbryoScope Unisense FertiliTech, Denmark) for presence and persistence of multinucleation. All embryos were checked again via video review at ESHRE Concensus proposed embryo evaluating times (231h, 261h, 441h). 145 patients had multinucleated embryo transfer (group 1) and 366 patients had no multinucleated embryo transfer (group 2). RESULTS: There were no significant differences (p>0.05) in age, BMI, number of oocyte retrieved, number of IVF attempt, day 3 FSH, indication for IVF and frequency of single vs double embryo transfer between the groups. Group 1 have significantly lower clinical pregnancy rate (23.4% vs 44.0%, p>0.001) and lower implantation rate (23.3% vs 43.6%, p>0.001) compared to group 2. In multivariate analysis only patients age (p¼0.001, OR¼0.95 CI¼(0.92-0.98)) and presence of multinucleation (p<0.001 OR¼0.37, CI¼(0.24-0.56)) were the only significant predictors of clinical pregnancy rate. Despite the importance of multinucleation, only 27.7% (44/159) of the embryos with multinucleation can be detected with conventional control timing of the embryos which was proposed by ESHRE consensus. The remaining 73.2% (115/159) embryos with multinucleation have duration of multinucleation out of the proposed embryo check time intervals. CONCLUSION: Multinucleation can not always be detected by conventional control timings. The time-lapse monitoring system is the only available tool to identify all cases with multinucleation which significantly decrease pregnancy rates.
CONCLUSION: We have demonstrated a positive relationship between a high ICM score and a greater BW. By definition, a grade A ICM has more cells than a grade B ICM, so it may be that advanced cell propagation in the pre–implantation embryo persists through the fetal period. Advanced TE proliferation may not substantially contribute to fetal growth, although some trends may become significant as the study size increases. O-230 Tuesday, October 15, 2013 05:45 PM EMBRYOS REACHING THE MORULA STAGE BEFORE 70 HOURS POST-ICSI PRESENT HIGHER IMPLANTATION RATES. I. Rubio, J. Herrero, A. Tejera, J. Giles, J. M. De los Santos, M. Meseguer. Instituto Valenciano de Infertilidad (IVI Valencia), Valencia, Spain. OBJECTIVE: To analyze the influence of early morula formation (EtM) on the implantation success. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: There were included 3532 couples on their first-second ICSI from the oocyte donation program at IVI Valencia. The development of the resulting embryos was monitored with a time-lapse system. From all the embryos transferred, 3782 with known implantation (0 or 100%) were selected for further analysis. The time point for morula formation (tM) was defined as when blastomere shape was not visible and full embryo compaction was achieved; early morula formation (EtM) was considered when that phenomenon occurs before 70 hours post ICSI. RESULTS: Data about incidence and implantation rate for the 3782 embryos considered are shown in Table 1. TABLE 1. Incidence, IR and tM in the population analyzed No EtM (day 3 transfer)
O-229 Tuesday, October 15, 2013 05:30 PM PRE-IMPLANTATION BLASTOCYST MORPHOLOGY PREDICTS BIRTH WEIGHT. F. Licciardi,a D. McCulloh,a C. Schmidt-Sarosi,a C. Oh.b aObstetrics and Gynecology, NYU Langone Medical Center, New York, NY; bBiostatistics, Population Health, NYU Langone Medical Center, New York, NY. OBJECTIVE: Placental and fetal development are dependent on the potential bestowed upon them by the early embryo. We theorized that morphological signs of embryo vigor may predict birth weight. DESIGN: Retro Cohort. MATERIALS AND METHODS: 140 births from fresh SET autologous blasts were analyzed; outcome variables included birth weight(BW),gestational age(GA)and gender. Univariate linear regression was used to control for the natural association between BW and GA. Measured blast variables were stage and score of the ICM and TE. RESULTS: Blast stage and the grade of the TE were not related to BW. The grade of the ICM, however, did predict BW. Newborns who had an ICM grade of A were significantly heavier than those with an ICM grade of B. No blast variable was related to GA or gender.
BW Mean (SD) Gest Age Gender Blast Stage 1 (n¼3) 2 (n¼6) 3 (n¼17) 4 (n¼114) Grade ICM A (n¼42) B (n¼90) C (n¼3) Grade Trph a (n¼29) b (n¼101) c (n¼5)
S70
male female 4 4 vs 1 4 vs 2 4 vs 3 4 vs 1,2,3 A A vs B A vs C A vs BC a a vs b a vs c a vs bc
ASRM Abstracts
3245.47 (481.3) 3139.8 (502.5) 3231.7 (486.3) 3363.3 (285.4) 3151 (312.4) 2940.8 (591.1) 3041.9 (518.5) 3348.8 (456.0) 3126.7 (511.7) 2938.3 (263.1) 3120.4 (505.6) 3248.2 (483.8) 3187.5 (513.1) 2976.2 (304.1) 3177.1 (505.9)
EtM (day 3 transfer)
p-value
Incidence (N¼2776) 97.03% [96.41-97.65] (N¼85) 2.97% [2.35-3.59] [CI 95%] IR 26.59% [24.94-28.23] 37.65% [27.13-48-16] 0.024 [CI 95%] tM 65.97h [64.97-66.98] [CI 95%]
The time of each cleavage times of the embryos [the first division to 2 cells (t2), second (3 cells, t3), third (4 cells, t4), fourth (5 cells, t5), fifth (6 cells, t6), sixth (7 cells, t7), seventh (8 cells, t8) and eighth (9 cells, t9)] were shorter in EtM embryos, reaching each stage earlier. We observed that 100% of the EtM embryos became previously an 8-cells stage on day 3 transfers vs. 88% of no EtM, p<0.05. There were no differences in terms of other potential confusion variables as fragmentation grade, maternal age, stimulation length, oocytes retrieved, mature oocytes retrieved, number of embryos transferred and number of frozen embryos. CONCLUSION: We founded higher IR in the group of embryos that reached the morula stage before 70 hours post-ICSI on day 3 transferences. These data suggest that the EtM, easily detectable by time-lapse systems, is a consistent good prognosis marker to select embryos for transfer and may improve the subsequent reproductive outcome.
p-value (univariate linear regression on BW) 23.77. (2.76)/<0.001 105.68 (83.4)/ 0.21 Adjusted p-value for GA Reference 131.6 (287.8)/ 0.65 -80.7 (206.2)/ 0.69 -290.9 (131.6)/ 0.03 -189.7 (109.08)/ 0.08 Reference -222.13 (93.3)/ 0.02 -410.5 (294.1)/ 0.17 -228.5 (92.6)/ 0.02 Reference -60.740 (107.61)/ 0.573 -272.01 (243.54)/ 0.266 -71.09 (106.959)/ 0.507
0.620 0.874 0.032 0.115 0.025 0.079 0.018 0.847 0.206 0.744
Vol. 100, No. 3, Supplement, September 2013
CONCLUSION: We have demonstrated a positive relationship between a high ICM score and a greater BW. By definition, a grade A ICM has more cells than a grade B ICM, so it may be that advanced cell propagation in the pre–implantation embryo persists through the fetal period. Advanced TE proliferation may not substantially contribute to fetal growth, although some trends may become significant as the study size increases. O-230 Tuesday, October 15, 2013 05:45 PM EMBRYOS REACHING THE MORULA STAGE BEFORE 70 HOURS POST-ICSI PRESENT HIGHER IMPLANTATION RATES. I. Rubio, J. Herrero, A. Tejera, J. Giles, J. M. De los Santos, M. Meseguer. Instituto Valenciano de Infertilidad (IVI Valencia), Valencia, Spain. OBJECTIVE: To analyze the influence of early morula formation (EtM) on the implantation success. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: There were included 3532 couples on their first-second ICSI from the oocyte donation program at IVI Valencia. The development of the resulting embryos was monitored with a time-lapse system. From all the embryos transferred, 3782 with known implantation (0 or 100%) were selected for further analysis. The time point for morula formation (tM) was defined as when blastomere shape was not visible and full embryo compaction was achieved; early morula formation (EtM) was considered when that phenomenon occurs before 70 hours post ICSI. RESULTS: Data about incidence and implantation rate for the 3782 embryos considered are shown in Table 1. TABLE 1. Incidence, IR and tM in the population analyzed No EtM (day 3 transfer)
O-229 Tuesday, October 15, 2013 05:30 PM PRE-IMPLANTATION BLASTOCYST MORPHOLOGY PREDICTS BIRTH WEIGHT. F. Licciardi,a D. McCulloh,a C. Schmidt-Sarosi,a C. Oh.b aObstetrics and Gynecology, NYU Langone Medical Center, New York, NY; bBiostatistics, Population Health, NYU Langone Medical Center, New York, NY. OBJECTIVE: Placental and fetal development are dependent on the potential bestowed upon them by the early embryo. We theorized that morphological signs of embryo vigor may predict birth weight. DESIGN: Retro Cohort. MATERIALS AND METHODS: 140 births from fresh SET autologous blasts were analyzed; outcome variables included birth weight(BW),gestational age(GA)and gender. Univariate linear regression was used to control for the natural association between BW and GA. Measured blast variables were stage and score of the ICM and TE. RESULTS: Blast stage and the grade of the TE were not related to BW. The grade of the ICM, however, did predict BW. Newborns who had an ICM grade of A were significantly heavier than those with an ICM grade of B. No blast variable was related to GA or gender.
BW Mean (SD) Gest Age Gender Blast Stage 1 (n¼3) 2 (n¼6) 3 (n¼17) 4 (n¼114) Grade ICM A (n¼42) B (n¼90) C (n¼3) Grade Trph a (n¼29) b (n¼101) c (n¼5)
S70
male female 4 4 vs 1 4 vs 2 4 vs 3 4 vs 1,2,3 A A vs B A vs C A vs BC a a vs b a vs c a vs bc
ASRM Abstracts
3245.47 (481.3) 3139.8 (502.5) 3231.7 (486.3) 3363.3 (285.4) 3151 (312.4) 2940.8 (591.1) 3041.9 (518.5) 3348.8 (456.0) 3126.7 (511.7) 2938.3 (263.1) 3120.4 (505.6) 3248.2 (483.8) 3187.5 (513.1) 2976.2 (304.1) 3177.1 (505.9)
EtM (day 3 transfer)
p-value
Incidence (N¼2776) 97.03% [96.41-97.65] (N¼85) 2.97% [2.35-3.59] [CI 95%] IR 26.59% [24.94-28.23] 37.65% [27.13-48-16] 0.024 [CI 95%] tM 65.97h [64.97-66.98] [CI 95%]
The time of each cleavage times of the embryos [the first division to 2 cells (t2), second (3 cells, t3), third (4 cells, t4), fourth (5 cells, t5), fifth (6 cells, t6), sixth (7 cells, t7), seventh (8 cells, t8) and eighth (9 cells, t9)] were shorter in EtM embryos, reaching each stage earlier. We observed that 100% of the EtM embryos became previously an 8-cells stage on day 3 transfers vs. 88% of no EtM, p<0.05. There were no differences in terms of other potential confusion variables as fragmentation grade, maternal age, stimulation length, oocytes retrieved, mature oocytes retrieved, number of embryos transferred and number of frozen embryos. CONCLUSION: We founded higher IR in the group of embryos that reached the morula stage before 70 hours post-ICSI on day 3 transferences. These data suggest that the EtM, easily detectable by time-lapse systems, is a consistent good prognosis marker to select embryos for transfer and may improve the subsequent reproductive outcome.
p-value (univariate linear regression on BW) 23.77. (2.76)/<0.001 105.68 (83.4)/ 0.21 Adjusted p-value for GA Reference 131.6 (287.8)/ 0.65 -80.7 (206.2)/ 0.69 -290.9 (131.6)/ 0.03 -189.7 (109.08)/ 0.08 Reference -222.13 (93.3)/ 0.02 -410.5 (294.1)/ 0.17 -228.5 (92.6)/ 0.02 Reference -60.740 (107.61)/ 0.573 -272.01 (243.54)/ 0.266 -71.09 (106.959)/ 0.507
0.620 0.874 0.032 0.115 0.025 0.079 0.018 0.847 0.206 0.744
Vol. 100, No. 3, Supplement, September 2013