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Preimplantation genetic screening (PGS) with next generation sequencing (NGS) achieves ongoing pregnancy with fewer transfers and total miscarriages compared to non-PGS cycles
10% vs. 11%), 38-40 (Av. 17%, 16% vs. 17%), 41-42 (Av. 28%, 27% vs. 29%), and >42 years old (Av. 44%, 40% vs. 46%). Polyploidy was identical for every age group and lab (1%). Instead mosaicism rates were in general higher in lab 1 vs lab 2 with egg donor being 18% vs. 13% (Av. 16%), <35 years old (Av. 18%, 23% vs. 14%), 35-37 (Av. 17%, 21% vs. 13%), 38-40 (Av. 13%, 17% vs. 10%), 41-42 (Av. 10%, 13% vs. 8%), and >42 years old (Av. 8%, 11% vs. 5%). Average euploidy rates were 59%, 53%, 44% 31%, 19% and 14%, respectively. CONCLUSIONS: Differences between labs in mosaic incidence can be attributed to scoring criteria. The etiology of mosaicism is in mitosis; hence apparent age-associated decreases can be attributed to an increase in aneuploid classification. Sufficient obstetric outcomes from transferred mosaics are forthcoming, thus standardizing scoring criteria and providing clinical implications is premature. The observed correlation between maternal age and incidence of aneuploidy, at near identical rates, between independent centers demonstrates high levels of reproducibility. The results herein can be used to counsel patients and guide expectations. References: 1. Validation of blastocyst biopsy and next generation sequencing (NGS) for the purpose of preimplantation genetic screening (PGS)Kung, A. et al.Fertility and Sterility, Volume 102, Issue 3, e96 2. Next generation sequencing (NGS) for preimplantation genetic screening (PGS) discovers mosaicism is independent of ageEscudero, Tomas et al.Fertility and Sterility , Volume 105 , Issue 2 , e19 3. Chromosome mosaicism in human embryos.Munne S1, Weier HU, Grifo J, Cohen J. Biol Reprod. 1994 Sep;51(3):373-9.
with no blastocyst stage embryos were excluded. Cumulative OP/LBRs were calculated per retrieval including up to 4 transfers and analyzed by age-group. IVF/PGS cycles with no euploid embryos available for transfer were included. Secondary outcomes included the number of embryos transferred per cycle, cumulative OP/LBR after the first embryo transfer (ET), and cumulative spontaneous abortion rate (SABR) per clinical pregnancy. Statistical analysis was performed using Fisher’s exact test with P<0.05 considered significant. RESULTS: 2547 cycles meeting inclusion criteria were identified. 844 retrievals and 525 FET cycles were performed in the PGS with NGS group. In the no PGS group, there were 953 retrievals and 225 FET cycles. 242 retrieval cycles did not form blastocysts and were excluded. The number of embryos transferred per cycle was significantly higher in the no PGS group than the PGS with NGS group (1.580.69 vs 1.010.11, p<0.001). Primary and secondary outcomes are summarized in the table. Per retrieval, there was no statistical difference in cumulative OP/LBR between groups. Pregnancy was achieved more often after the first transfer in women 38-40 years old. The cumulative OP/LBR per retrieved patient with embryos available for transfer was significantly higher for the PGS group over age 35. The cumulative SABR was significantly higher for ages 38-42yo in the no PGS group. CONCLUSION: Overall, cumulative OP/LBRs are similar in women undergoing IVF with or without PGS, but IVF cycles without PGS have significantly more embryos transferred per cycle. Retrievals utilizing PGS with NGS result in OP/LB with fewer embryo transfers in women 38-40 years old and fewer miscarriages in women ages 38-42. O-47 Monday, October 30, 2017 12:00 PM
O-46 Monday, October 30, 2017 11:45 AM PREIMPLANTATION GENETIC SCREENING (PGS) WITH NEXT GENERATION SEQUENCING (NGS) ACHIEVES ONGOING PREGNANCY WITH FEWER TRANSFERS AND TOTAL MISCARRIAGES COMPARED TO NON-PGS CYCLES. S. M. Maxwell, D. H. McCulloh, H. Lee, A. S. Berkeley, J. Grifo. OB/GYN, New York University Fertility Center, New York, NY.
THE CHALLENGE OF POLYPLOIDY AND COMPREHENSIVE CHROMOSOME SCREENING: VALIDATION OF A TARGETED NEXT GENERATION SEQUENCING (TNGS) PLATFORM FOR DETECTION OF TRIPLOIDY IN HUMAN BLASTOCYSTS. D. Marin,a,b R. S. Zimmerman,c X. Tao,c Y. Zhan,c R. T. Scott, Jr.,a,b N. Treff.a,b aIVI/RMA, Basking Ridge, NJ; bThomas Jefferson University, Philadelphia, PA; cFoundation for Embryonic Competence, Basking Ridge, NJ.
OBJECTIVE: To determine the cumulative ongoing pregnancy/live birth rates (OP/LBR) of PGS cycles with NGS compared to non-PGS cycles using an intention to treat analysis. DESIGN: Cohort Study MATERIAL AND METHODS: All patients undergoing an oocyte retrieval for IVF or IVF/PGS with NGS and their subsequent frozen embryo transfer (FET) cycles at a single university-based fertility center were collected from 1/2014 through 7/2016. Embryo banking cycles, donor oocyte cycles, cycles utilizing PGS with array comparative genomic hybridization, and IVF cycles
OBJECTIVE: Current NGS-based CCS platforms perform an initial whole genome amplification step, which prevents simultaneous genotyping due to shallow sequencing depth. Therefore, triploidy detection by NGS remains challenging and has only been reported based on sex chromosome copy number ratios, which fail to account for XXX triploids, and may be prone to misdiagnosis due to sample contamination or technological artefacts. Using genotyping data generated in parallel with copy number analysis from a tNGS-based CCS platform, this study aims to validate triploidy detection in human blastocysts as well as its frequency and parental origin.
Cumulative OP/LBR Per Retrieval (%) by age <35 35-37 38-40 41-42 >42 OP/LBR after 1st ET per Retrieval (%) by age <35 35-37 38-40 41-42 >42 Cumulative OP/LBR per retrieved patient with embryos available for transfer (%) by age <35 35-37 38-40 41-42 >42 Cumulative SABR per clinical pregnancy (%) by age <35 35-37 38-40 41-42 >42
e20
ASRM Abstracts
PGS with NGS
No PGS
P- value
62.6% (97/155) 50.3% (86/171) 42.4% (109/257) 17.9% (29/162) 7.1% (7/98) PGS with NGS 54.2% (84/155) 45.6% (78/171) 39.3% (101/257) 16% (26/162) 6.1% (6/98) PGS with NGS
70.1% (169/241) 53.8% (78/145) 38% (62/163) 21.1% (15/71) 10.3% (8/78) No PGS 47.3% (114/241) 40.7% (59/145) 29.4% (48/163) 18.3% (13/71) 9% (7/78) No PGS
0.15 0.61 0.43 0.68 0.64 P- value 0.22 0.44 0.049 0.8 0.66 P-value
74.6% (97/130) 71.1% (86/121) 70.8% (109/154) 67.4% (29/43) 46.7% (7/15) PGS with NGS
70.1% (169/241) 53.8% (78/145) 38% (62/163) 21.1% (15/71) 10.3% (8/78) no PGS
0.43 0.006 <0.001 <0.001 0.004 P- value
10.2% (11/108) 14.9% (15/101) 11.7% (14/120) 14.7% (5/34) 12.5% (1/8)
14.5% (28/193) 20.4% (20/98) 28.6% (24/84) 46.4% (13/28) 55.6% (10/18)
0.37 0.36 0.004 0.013 0.1
Vol. 108, No. 3, Supplement, September 2017
with no blastocyst stage embryos were excluded. Cumulative OP/LBRs were calculated per retrieval including up to 4 transfers and analyzed by age-group. IVF/PGS cycles with no euploid embryos available for transfer were included. Secondary outcomes included the number of embryos transferred per cycle, cumulative OP/LBR after the first embryo transfer (ET), and cumulative spontaneous abortion rate (SABR) per clinical pregnancy. Statistical analysis was performed using Fisher’s exact test with P<0.05 considered significant. RESULTS: 2547 cycles meeting inclusion criteria were identified. 844 retrievals and 525 FET cycles were performed in the PGS with NGS group. In the no PGS group, there were 953 retrievals and 225 FET cycles. 242 retrieval cycles did not form blastocysts and were excluded. The number of embryos transferred per cycle was significantly higher in the no PGS group than the PGS with NGS group (1.580.69 vs 1.010.11, p<0.001). Primary and secondary outcomes are summarized in the table. Per retrieval, there was no statistical difference in cumulative OP/LBR between groups. Pregnancy was achieved more often after the first transfer in women 38-40 years old. The cumulative OP/LBR per retrieved patient with embryos available for transfer was significantly higher for the PGS group over age 35. The cumulative SABR was significantly higher for ages 38-42yo in the no PGS group. CONCLUSION: Overall, cumulative OP/LBRs are similar in women undergoing IVF with or without PGS, but IVF cycles without PGS have significantly more embryos transferred per cycle. Retrievals utilizing PGS with NGS result in OP/LB with fewer embryo transfers in women 38-40 years old and fewer miscarriages in women ages 38-42. O-47 Monday, October 30, 2017 12:00 PM
O-46 Monday, October 30, 2017 11:45 AM PREIMPLANTATION GENETIC SCREENING (PGS) WITH NEXT GENERATION SEQUENCING (NGS) ACHIEVES ONGOING PREGNANCY WITH FEWER TRANSFERS AND TOTAL MISCARRIAGES COMPARED TO NON-PGS CYCLES. S. M. Maxwell, D. H. McCulloh, H. Lee, A. S. Berkeley, J. Grifo. OB/GYN, New York University Fertility Center, New York, NY.
THE CHALLENGE OF POLYPLOIDY AND COMPREHENSIVE CHROMOSOME SCREENING: VALIDATION OF A TARGETED NEXT GENERATION SEQUENCING (TNGS) PLATFORM FOR DETECTION OF TRIPLOIDY IN HUMAN BLASTOCYSTS. D. Marin,a,b R. S. Zimmerman,c X. Tao,c Y. Zhan,c R. T. Scott, Jr.,a,b N. Treff.a,b aIVI/RMA, Basking Ridge, NJ; bThomas Jefferson University, Philadelphia, PA; cFoundation for Embryonic Competence, Basking Ridge, NJ.
OBJECTIVE: To determine the cumulative ongoing pregnancy/live birth rates (OP/LBR) of PGS cycles with NGS compared to non-PGS cycles using an intention to treat analysis. DESIGN: Cohort Study MATERIAL AND METHODS: All patients undergoing an oocyte retrieval for IVF or IVF/PGS with NGS and their subsequent frozen embryo transfer (FET) cycles at a single university-based fertility center were collected from 1/2014 through 7/2016. Embryo banking cycles, donor oocyte cycles, cycles utilizing PGS with array comparative genomic hybridization, and IVF cycles
OBJECTIVE: Current NGS-based CCS platforms perform an initial whole genome amplification step, which prevents simultaneous genotyping due to shallow sequencing depth. Therefore, triploidy detection by NGS remains challenging and has only been reported based on sex chromosome copy number ratios, which fail to account for XXX triploids, and may be prone to misdiagnosis due to sample contamination or technological artefacts. Using genotyping data generated in parallel with copy number analysis from a tNGS-based CCS platform, this study aims to validate triploidy detection in human blastocysts as well as its frequency and parental origin.
Cumulative OP/LBR Per Retrieval (%) by age <35 35-37 38-40 41-42 >42 OP/LBR after 1st ET per Retrieval (%) by age <35 35-37 38-40 41-42 >42 Cumulative OP/LBR per retrieved patient with embryos available for transfer (%) by age <35 35-37 38-40 41-42 >42 Cumulative SABR per clinical pregnancy (%) by age <35 35-37 38-40 41-42 >42
e20
ASRM Abstracts
PGS with NGS
No PGS
P- value
62.6% (97/155) 50.3% (86/171) 42.4% (109/257) 17.9% (29/162) 7.1% (7/98) PGS with NGS 54.2% (84/155) 45.6% (78/171) 39.3% (101/257) 16% (26/162) 6.1% (6/98) PGS with NGS
70.1% (169/241) 53.8% (78/145) 38% (62/163) 21.1% (15/71) 10.3% (8/78) No PGS 47.3% (114/241) 40.7% (59/145) 29.4% (48/163) 18.3% (13/71) 9% (7/78) No PGS
0.15 0.61 0.43 0.68 0.64 P- value 0.22 0.44 0.049 0.8 0.66 P-value
74.6% (97/130) 71.1% (86/121) 70.8% (109/154) 67.4% (29/43) 46.7% (7/15) PGS with NGS
70.1% (169/241) 53.8% (78/145) 38% (62/163) 21.1% (15/71) 10.3% (8/78) no PGS
0.43 0.006 <0.001 <0.001 0.004 P- value
10.2% (11/108) 14.9% (15/101) 11.7% (14/120) 14.7% (5/34) 12.5% (1/8)
14.5% (28/193) 20.4% (20/98) 28.6% (24/84) 46.4% (13/28) 55.6% (10/18)
0.37 0.36 0.004 0.013 0.1
Vol. 108, No. 3, Supplement, September 2017