24 CHROMOSOME ANEUPLOIDY SCREENING AND FET ALLOWS FOR HIGH PREGNANCY RATES AND THE OPPORTUNITY FOR ELECTIVE SINGLE EMBRYO TRANSFER Proctor, J. Glenn Wilson, J. Michael Swanson, Michael S. Bush, Mark R. Introduction • Blastocysts culture allows for developmental selection of the embryo cohort and 24 chromosome aneuploidy screening further defines those embryos capable of becoming a healthy live born. • 24 chromosome aneuploidy screening is applied with FET to maximize clinical outcome. • Clinical outcomes are high for many patients diagnosed with decreased ovarian reserve, as defined by an AMH less than 1.5. Literature Comparison: Frozen Versus Fresh Embryo Transfer Outcome Parameter Frozen ET Frozen ET Better Than Equal to Fresh Fresh Frozen ET Worse Than Fresh # Studies Reviewed Clinical Pregnancy Rate 8 3 0 11 Implantation Rate 7 3 0 10 Ectopic Rate 3 0 0 3 Miscarriage Rate 1 0 0 1 Birth Defects 0 1 0 1 Perinatal Complications 2 1 0 3 Twin Rate 1 1 0 2 Kiehl, M.; Natera 10.13 Why Comprehensive Chromosome Screening? • • • • • • • Advanced maternal age Repeated IVF cycles Recurrent pregnancy loss Prior pregnancy with a chromosome abnormality Gender selection Ability to screen prior frozen embryos Decrease the odds of a chromosome abnormality in a live born 24-Chromosome Screening • Conceptions uses a SNP array platform o o o o Whole chromosome abnormalities (trisomies and monosomies) Polyploidy Uniparental disomy Large deletions or duplications • Cost effective for the patients o Large percentage of patients utilizing technology lowers IVF package costs o Eliminates ET and medication fees if all aneuploidy • Ability to confirm parentage • Ability to detect DNA contamination Live Birth outcome with trophectoderm biopsy, blast vitrification, and single-nucleotide polymorphism microarray-based comprehensive chromosome screening in infertile patients Schoolcraft et al.; Fertil Steril; Vol. 96, No. 3, Sept. 2011 • The combination of TE biopsy, blastocyst vitrification, and SNP microarray – based CCS technology results in: o High implantation rates o Low miscarriage rates o The realization of the expected benefit of aneuploidy screening in ART Methods • Retrospective cohort study. 396 patients undergoing IVF from 10-1-2010 thru 1-1-2014 at Conceptions in Colorado were offered a CCS cycle with subsequent FET. • These data include all patients that desired to use their own oocytes with ICSI. • Embryos were cultured in sequential media to day 5 or 6, hatched, and laser biopsied. • Biopsied embryos were vitrified using a closed system and stored for subsequent FET. • SNP analysis was performed by Natera (San Carlos, CA). • 1-2 embryos were warmed at a later date when the uterine environment was optimal Uterine Preparation for Transfer • BCP, lupron overlap in preceding month • With menses, baseline ultrasound for ovarian cysts, p4/ e2 • If clear, start vivelle dot 1/2/4 (1 dot for 6 days, 2 dots for 4 days, 4 dots for 4 days, then back down to 2 dots) + estrace 2mg PO BID from day 1 • Day 5 lining check, e2, dose adjustments as needed, including consideration of vaginal estrace • Day 10 lining check, e2 > 300, 5K trigger if lining >/= to 8 mm and triple layer • Start PIO at 50/d day after trigger, then 75/d from 2 days after trigger • FET CCS blast transfer 6 days after trigger Results Conceptions Reproductive Associates - Littleton, CO 10/1/2010 – 1/1/2014 Patient Age <35 35-37 38-40 41-42 43-44 Number of transfers (total = 396) Percentage of transfers resulting in pregnancies (FHT) 156 106 86 74.4% 77.4% 61.6% 71.0% 82.4% Percent with single embryo transfer 65.4% 72.6% 76.7% 77.4% 88.2% Implantation Rate 70.1% 74.1% 58.1% 71.1% 78.9% Average number of embryos transferred 1.35 1.27 1.22 Percentage of patients with AMH < 1.5 27.1% 39.4% 37.7% 68.0% 80.0% Percent aneuploidy (Patients with ET) 21.3% 29.0% 38.4% 42.0% 34.3% 31 1.23 17 1.12 Pregnancy Rates (FHT) 90.0% 80.0% 70.0% 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% 0.0% < 35 (156) 35-37 (106) 38-40 (86) 41-42 (31) 43-44 (17) CCS Allows for Fewer Embryos Transferred % SET # Embryos Transferred 1.12 1.35 < 35 35-37 38-40 1.23 1.27 1.22 41-42 43-44 100.0% 90.0% 80.0% 70.0% 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% 0.0% < 35 35-37 38-40 41-42 43-44 Implantation Rates 90.0% 80.0% 70.0% 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% 0.0% < 35 35-37 38-40 41-42 43-44 Percent Aneuploidy (Patients with ET) 45.0% 40.0% 35.0% 30.0% 25.0% 20.0% 15.0% 10.0% 5.0% 0.0% < 35 35-37 38-40 41-42 43-44 Percentage of Patients with AMH< 1.5 90.0% 80.0% 70.0% 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% < 35 35-37 38-40 41-42 43-44 Percentage of Patients with a Biopsy but No Euploid 50.0% 48.3% 50.0% 40.0% 30.0% 20.0% 10.0% 14.0% 20.6% 5.8% 0.0% < 35 35-37 38-40 41-42 43-44 Percentage of Patients with No Biopsy Due to D5 Development Age < 35 35 - 37 38 - 40 41 – 42 43 -44 % No Bxy 12.3 % 15.5 % 19.1 % 37.0% 23.1 % • Due to arrest from day 3 to 5 • Poor quality blastocyst development • Patients electing to discontinue biopsy testing Conclusion • 24 chromosome aneuploidy screening with vitrification allows patients the opportunity to obtain embryos with high reproductive potential while ensuring endometrial synchrony. • A percentage of embryos were aneuploidy, particularly women of advanced reproductive age and/or possessing decreased ovarian reserve. • Identifying aneuploid embryos before transfer allows for the elimination of many causes of failed IVF, including miscarriage and abnormal amniocentesis. • Chromosome screening allows for patients with an AMH < 1.5 the ability to achieve a viable pregnancy utilizing elective single embryo transfer.