MATERNAL AGE:
PGD to improve ART outcome
<35 35-37 38-40 41-42
- Ongoing implantation (US average)* 31% 23% 13%
6%
- Abnormal embryos (array CGH)** 54% 67% 75% 82%
- Non-chromosomal implantation loss 15% 10% 12%
12%
IVF results compared to chromosome abnormalities
*estimated from SART (2011), ** Reprogenetics 2011 data
Time-lapse and aneuploidy:
Campbell et al. (2013)
Campbell et al. (2013) Reprod Biomed Online 26:477-85
• Chromosomally abnormal
embryos (by array CGH) had
delayed blastulation.
• NO correlation between any
other parameters and
aneuploidy
Time to blastulation (tB) x Time from
insemination to start of blastulation (tSB)
High rate false + and neg.
Norm Abn N
Low risk = 61% 39% 36
Med risk = 33% 67% 48
High risk = 0% 100% 11
Contradicting PGS results
using day 3 biopsy and FISH
Positive effect
Gianaroli et al. 1999
Munné et al 1999
Gianaroli et al 2001a
Gianaroli et al. 2001b
Munné et al. 2003
Gianaroli et al. 2004
Munné et al. 2005
Munné et al 2006
Verlinsky et al. 2005
Colls et al. 2007
Garrisi et al. 2009
Rubio et al. 2009
Rubio et al. 2013 *
No effect
Werlin et al. 2003 *
Staessen et al. 2004 *
Platteau et al. 2005 *
Jansen et al. 2008 *
Mersereau et al. 2008 *
Schoolcraft et al. 2009 *
Negative effect
Mastenbroek et al. 2007 *
Hardarson et al. 2008 *
* CRT
Effect of day 3 biopsy
and blastocyst biopsy
Scott et al. (2013) Fertil Steril, in press
Patients randomized to cleavage of blastocyst biopsy. Two best embryos randomized 1 to biopsy and
1 to no biopsy, both replaced. Biopsied embryos fingerprinted and compared with the fetus.
cleavage stage blastocyst
biopsy not biopsy not
Implantation rate 31% 53% 52% 54%
P<0.05
N.S.
(42% reduction)
…but biopsy is an operator-dependent procedure and its effect may vary
NormalTrisomy Monosomy
Normal
DNA
Embryo
DNA
Array Comparative
Genome Hybridization
aCGH eliminates the negative effect of maternal age
on implantation
Reprogenetics data. 819 cycles with follow up, 3726 embryos analyzed. Also observed with
CGH (Wells et al. ASRM 2010), SNPs (Forman et al. ASRM 2011) and qPCR (Scott et al. 2012)
0%
10%
20%
30%
40%
50%
60%
30-34 35-39 40-42
day 3
day 5
Implantationrate
Maternal age
Conclusions

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L6 keysslides

  • 1. MATERNAL AGE: PGD to improve ART outcome
  • 2. <35 35-37 38-40 41-42 - Ongoing implantation (US average)* 31% 23% 13% 6% - Abnormal embryos (array CGH)** 54% 67% 75% 82% - Non-chromosomal implantation loss 15% 10% 12% 12% IVF results compared to chromosome abnormalities *estimated from SART (2011), ** Reprogenetics 2011 data
  • 3. Time-lapse and aneuploidy: Campbell et al. (2013) Campbell et al. (2013) Reprod Biomed Online 26:477-85 • Chromosomally abnormal embryos (by array CGH) had delayed blastulation. • NO correlation between any other parameters and aneuploidy Time to blastulation (tB) x Time from insemination to start of blastulation (tSB) High rate false + and neg. Norm Abn N Low risk = 61% 39% 36 Med risk = 33% 67% 48 High risk = 0% 100% 11
  • 4. Contradicting PGS results using day 3 biopsy and FISH Positive effect Gianaroli et al. 1999 Munné et al 1999 Gianaroli et al 2001a Gianaroli et al. 2001b Munné et al. 2003 Gianaroli et al. 2004 Munné et al. 2005 Munné et al 2006 Verlinsky et al. 2005 Colls et al. 2007 Garrisi et al. 2009 Rubio et al. 2009 Rubio et al. 2013 * No effect Werlin et al. 2003 * Staessen et al. 2004 * Platteau et al. 2005 * Jansen et al. 2008 * Mersereau et al. 2008 * Schoolcraft et al. 2009 * Negative effect Mastenbroek et al. 2007 * Hardarson et al. 2008 * * CRT
  • 5. Effect of day 3 biopsy and blastocyst biopsy Scott et al. (2013) Fertil Steril, in press Patients randomized to cleavage of blastocyst biopsy. Two best embryos randomized 1 to biopsy and 1 to no biopsy, both replaced. Biopsied embryos fingerprinted and compared with the fetus. cleavage stage blastocyst biopsy not biopsy not Implantation rate 31% 53% 52% 54% P<0.05 N.S. (42% reduction) …but biopsy is an operator-dependent procedure and its effect may vary
  • 7. aCGH eliminates the negative effect of maternal age on implantation Reprogenetics data. 819 cycles with follow up, 3726 embryos analyzed. Also observed with CGH (Wells et al. ASRM 2010), SNPs (Forman et al. ASRM 2011) and qPCR (Scott et al. 2012) 0% 10% 20% 30% 40% 50% 60% 30-34 35-39 40-42 day 3 day 5 Implantationrate Maternal age