- Email: [email protected]
A logistic regression model to predict chromosomal normality through embryokinetics
Following ICSI, hours for embryos to reach the 2,3,4,5,6,7,8, 9+cell, morula, expanded and hatched blastocyst stage were recorded and compared between treatments. Data are presented as mean standard deviation, analysed using T-test and found to be significant if p<0.05. RESULTS: a) Embryos derived from SSR sperm had significantly delayed morula formation (9312 vs 9713hpi,p¼0.045), and blastocyst hatching (1199 vs 12813hpi,p¼0.03), yet were faster at reaching the two cell stage (28.55.0 vs 26.93. 9hpi, p¼0.03) compared to fresh ejaculated sperm (fresh vs SSR respectively). b) Younger patients reached the morula (92.911 vs 98.814hpi,p¼0.03), expanded blastocyst (111.78.4 vs 1188. 8hpi, p¼0.008) and hatched blastocyst (115.17.5 vs 12910. 7hpi, p<0.001) stages faster than older patients (younger vs older respectively). c) Morphokinetics were not affected by genetic outcome. CONCLUSION: This study supports that sperm source and maternal age contribute to embryo morphokinetics. To our knowledge, this is the first study to assess the effect of sperm origin on embryo morphokinetics. The results of this study are suggestive of the role of sperm in first cleavage and embryo development after embryonic genome activation. O-21 Monday, October 14, 2013 04:30 PM A LOGISTIC REGRESSION MODEL TO PREDICT CHROMOSOMAL NORMALITY THROUGH EMBRYOKINETICS. N. Basile,a M. d. C. Nogales,a E. Martınez,a M. Ariza,a M. Florensa,b M. Meseguer.c a IVI Madrid, Madrid, Spain; bIVI Barcelona, Barcelona, Spain; cIVI Valencia, Valencia, Spain. OBJECTIVE: After the introduction of time-lapse technology the objective of this study was to analyze the kinetics of chromosomally normal and abnormal embryos and to propose a logistic regression model to identify the most relevant kinetic variables associated with a normal chromosomal content. DESIGN: Consecutive prospective cohort study. March 2011 - August 2012. MATERIALS AND METHODS: Embryo development from 77 patients (n¼508) was analyzed with time-lapse imaging. Embryo biopsy took place on day 3 and chromosomal analysis was performed through array-comparative genome hybridization (CGH). The time for each embryo division was defined as t2 (time to 2 cells), t3 (3 cells), t4 (4 cells) and t5 (5 cells). Intervals between cleavages included cc2¼t3-t2 and cc3¼ t5-t3. We defined the second synchrony (s2¼t4-t3) and the interval between 2 and 5 cells as t5-t2. RESULTS: A logistic regression analysis was used to select and organize which observed timing events should be used together to select embryos with higher probability of being chromosomally normal. The model identified t5t2 OR ¼ 3.283 (95%CI 1.567-6.877) followed by cc3 OR¼ 1.383 (95%CI 0.756-2.527) and T5 OR¼ 5.275 (95%CI 1.892-14.70) as the most relevant variables related to a normal chromosomal content.. A ROC curve analysis to determine the predictive properties of this model with respect to chromosomal normality gave an AUC value of 0.634 (95% CI 0.581–0.687). An algorithm for embryo selection based on these three variables classified embryos from A+ to D- with significant differences in the percentage of normal embryos. More specifically: A+: 36.3%; A: 33.9%; B+: 32.0%; B: 19.5%; C+: 14.3%; C: 11.5%; D+: 10.0%; D: 9.0% (p < 0.001). CONCLUSION: The model gives rise to an algorithm that increases the probability of selecting chromosomally normal embryos when PGD is not available, although this by no means replaces such technique. Limitations regarding mosaicism and embryo selection prior to the biopsy should be considered.
O-22 Monday, October 14, 2013 04:45 PM THE EFFECTS OF ELEVATED SERUM PROGESTERONE LEVEL AT THE DAY OF HCG INJECTION ON CLINICAL OUTCOME IN IVF-ET PATIENTS. M. Li, Y. Xie, H. Park, A. Kumar, G. Hubert, R. Buyalos. Fertility and Surgical Associates of California, Thousand Oaks, CA. OBJECTIVE: To determine the effects of elevated serum progesterone (P4) at the day of hCG trigger on the clinical outcomes following IVF-ET. DESIGN: Retrospective case control study. MATERIALS AND METHODS: We reviewed 655 IVF-ET cycles. The thresholds of serum P4 were set at 1.4, 2.0 and 2.5 ng/ml. Patients with a level
FERTILITY & STERILITYÒ
of P4 less than the threshold were subjected to control group, and those higher than threshold were subjected to elevated p4 group. The clinical outcomes between two groups were compared. RESULTS: The total number of retrieved oocytes was significantly higher in elevated P4 group (18.810.8, 22.210.8 and 25.210.8) than in control(12.27.7, 14.09.1 and 14.89.5) (p¼0.000). The number of blastocysts was significantly higher in elevated P4 group (4.54.5, 5.6+5.5 and 6.25.9) than in control (2.73.1, 3.23.5 and 3.23.6) (p¼0.000). However, when the thresholds were set to 2.0 and 2.5ng/ml, the clinical pregnancy rate was lower in the elevated P4 group (41.6% and 37.3%) than in control (46.3% and 46.0%), but the difference were not statistically significant (p¼0.197and p¼0.144). Outcome of ET cycles in women with different P4 levels on the hCG day Number of cycles P4%1.4 P4>1.4 P value P4%2.0 P4>2.0 P value P4%2.5 P4>2.5 P value
321 (49%) 334 (51%) 523 (79.8%) 132 (20.2%) 604 (92.2%) 51 (7.8%)
Clinical pregnancy rate (%)
Total blastocyst number
Number of retrieved oocytes
Fertilization rate (%)
44.5 46.1 P¼0.374 46.3 41.7 P¼0.197
2.73.1 4.54.5 P¼0.000 3.23.5 5.65.5 P¼0.000
12.27.7 18.810.8 P¼0.000 14.09.1 22.210.8 P¼0.000
77.822 78.820 P¼0.054 79.421.2 74.219.5 P¼0.195
46.0 37.3 P¼0.144
3.23.6 6.25.9 P¼0.000
14.89.5 25.210.8 P¼0.000
78.621.1 76.119.6 P¼0.491
CONCLUSION: Our data demonstrated that higher serum P4 reflects good follicular recruitment and better chance of obtaining blastocysts. It also suggested that elevated P4 may adversely affect pregnancy rate. However, the difference was not sufficient to warrant a intervention such as deferring fresh embryo transfer and freezing embryos for future transfer.
O-23 Monday, October 14, 2013 05:00 PM SHOULD IMMATURE OOCYTES BE ROUTINELY ASSESSED FOR IN VITRO MATURATION AND UNDERGO ICSI DURING STIMULATED IVF CYCLES? J. N. Lillemon, Q. M. Halverson, J. Y. Lim, P. E. Patton, D. H. Wu. Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR. OBJECTIVE: After oocyte denudation, some metaphase I (MI) oocytes may undergo spontaneous in vitro maturation to reach metaphase II (MII) before ICSI. This study aims to determine the fertilization and blastocyst rates of in vitro matured (Late MII) oocytes compared to in vivo matured sibling MII oocytes in IVF-ICSI cycles. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Cycle parameters and outcomes of fresh autologous and donor-egg IVF-ICSI cycles from January 2012 to April 2013 were reviewed. Immediately after retrieval, oocytes were denuded, assessed for maturity, and cultured for 4–6 hours. ICSI was then performed on MII oocytes (Group 1) and MI oocytes that progressed to MII in vitro (Group 2). Embryos resulting from Group 2 were cultured separately to track their development. Fertilization and blastulation rates were compared between groups using chi-square and T-tests; logistic regression was used to control for potential confounders. RESULTS: A total of 1258 oocytes (Group 1¼1103, Group 2¼155) from 91 cycles that fit selection criteria were analyzed. There was no difference in the fertilization rate between Group 1 and 2 (84.0% vs. 86.5%, p¼0.44). Blastocyst development was significantly higher in Group 1 (43.8% vs. 29.9%, p<0.01), but blastocyst quality was similar- 56.7% of blastocysts in Group 1 and 57.5% in Group 2 were graded R3BB (p¼0.73). When isolating donor-egg cycles, similar fertilization (86.0% vs. 91.4%, p¼0.37) between groups and significantly higher blastulation in Group 1 (55.5% vs. 31.3%, p¼0.01) were also noted. Blastocyst development remained significantly higher in Group 1 after adjusting for age, BMI, infertility etiology, protocol, and peak estradiol (OR 2.06, 95% CI 1.28-3.30, p<0.01). CONCLUSION: Although Late MII oocytes can be normally fertilized after ICSI, their blastocyst development is significantly compromised.
S7
O-22 Monday, October 14, 2013 04:45 PM THE EFFECTS OF ELEVATED SERUM PROGESTERONE LEVEL AT THE DAY OF HCG INJECTION ON CLINICAL OUTCOME IN IVF-ET PATIENTS. M. Li, Y. Xie, H. Park, A. Kumar, G. Hubert, R. Buyalos. Fertility and Surgical Associates of California, Thousand Oaks, CA. OBJECTIVE: To determine the effects of elevated serum progesterone (P4) at the day of hCG trigger on the clinical outcomes following IVF-ET. DESIGN: Retrospective case control study. MATERIALS AND METHODS: We reviewed 655 IVF-ET cycles. The thresholds of serum P4 were set at 1.4, 2.0 and 2.5 ng/ml. Patients with a level
FERTILITY & STERILITYÒ
of P4 less than the threshold were subjected to control group, and those higher than threshold were subjected to elevated p4 group. The clinical outcomes between two groups were compared. RESULTS: The total number of retrieved oocytes was significantly higher in elevated P4 group (18.810.8, 22.210.8 and 25.210.8) than in control(12.27.7, 14.09.1 and 14.89.5) (p¼0.000). The number of blastocysts was significantly higher in elevated P4 group (4.54.5, 5.6+5.5 and 6.25.9) than in control (2.73.1, 3.23.5 and 3.23.6) (p¼0.000). However, when the thresholds were set to 2.0 and 2.5ng/ml, the clinical pregnancy rate was lower in the elevated P4 group (41.6% and 37.3%) than in control (46.3% and 46.0%), but the difference were not statistically significant (p¼0.197and p¼0.144). Outcome of ET cycles in women with different P4 levels on the hCG day Number of cycles P4%1.4 P4>1.4 P value P4%2.0 P4>2.0 P value P4%2.5 P4>2.5 P value
321 (49%) 334 (51%) 523 (79.8%) 132 (20.2%) 604 (92.2%) 51 (7.8%)
Clinical pregnancy rate (%)
Total blastocyst number
Number of retrieved oocytes
Fertilization rate (%)
44.5 46.1 P¼0.374 46.3 41.7 P¼0.197
2.73.1 4.54.5 P¼0.000 3.23.5 5.65.5 P¼0.000
12.27.7 18.810.8 P¼0.000 14.09.1 22.210.8 P¼0.000
77.822 78.820 P¼0.054 79.421.2 74.219.5 P¼0.195
46.0 37.3 P¼0.144
3.23.6 6.25.9 P¼0.000
14.89.5 25.210.8 P¼0.000
78.621.1 76.119.6 P¼0.491
CONCLUSION: Our data demonstrated that higher serum P4 reflects good follicular recruitment and better chance of obtaining blastocysts. It also suggested that elevated P4 may adversely affect pregnancy rate. However, the difference was not sufficient to warrant a intervention such as deferring fresh embryo transfer and freezing embryos for future transfer.
O-23 Monday, October 14, 2013 05:00 PM SHOULD IMMATURE OOCYTES BE ROUTINELY ASSESSED FOR IN VITRO MATURATION AND UNDERGO ICSI DURING STIMULATED IVF CYCLES? J. N. Lillemon, Q. M. Halverson, J. Y. Lim, P. E. Patton, D. H. Wu. Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR. OBJECTIVE: After oocyte denudation, some metaphase I (MI) oocytes may undergo spontaneous in vitro maturation to reach metaphase II (MII) before ICSI. This study aims to determine the fertilization and blastocyst rates of in vitro matured (Late MII) oocytes compared to in vivo matured sibling MII oocytes in IVF-ICSI cycles. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Cycle parameters and outcomes of fresh autologous and donor-egg IVF-ICSI cycles from January 2012 to April 2013 were reviewed. Immediately after retrieval, oocytes were denuded, assessed for maturity, and cultured for 4–6 hours. ICSI was then performed on MII oocytes (Group 1) and MI oocytes that progressed to MII in vitro (Group 2). Embryos resulting from Group 2 were cultured separately to track their development. Fertilization and blastulation rates were compared between groups using chi-square and T-tests; logistic regression was used to control for potential confounders. RESULTS: A total of 1258 oocytes (Group 1¼1103, Group 2¼155) from 91 cycles that fit selection criteria were analyzed. There was no difference in the fertilization rate between Group 1 and 2 (84.0% vs. 86.5%, p¼0.44). Blastocyst development was significantly higher in Group 1 (43.8% vs. 29.9%, p<0.01), but blastocyst quality was similar- 56.7% of blastocysts in Group 1 and 57.5% in Group 2 were graded R3BB (p¼0.73). When isolating donor-egg cycles, similar fertilization (86.0% vs. 91.4%, p¼0.37) between groups and significantly higher blastulation in Group 1 (55.5% vs. 31.3%, p¼0.01) were also noted. Blastocyst development remained significantly higher in Group 1 after adjusting for age, BMI, infertility etiology, protocol, and peak estradiol (OR 2.06, 95% CI 1.28-3.30, p<0.01). CONCLUSION: Although Late MII oocytes can be normally fertilized after ICSI, their blastocyst development is significantly compromised.
S7