24 CHROMOSOME ANEUPLOIDY SCREENING AND FET ALLOWS FOR OPPORTUNITY FOR ELECTIVE SINGLE

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.
`