1. Advanced age: Implantation problems
and miscarriages
Sesh Sunkara
Guy’s and St Thomas’ NHS Trust, London
King’s College London
2. Background
• Embryo implantation is complex involving
– Maturational events in the embryo
– Endometrium
– Maternal hormonal changes and immune responses
• IVF provides a unique opportunity in understanding
factors influencing embryo implantation
3. Maternal age and miscarriage
• Danish prospective register linked study
• All women with reproductive outcome from
1978 – 1992
• 634 272 women with 1 221 546 pregnancy
outcomes
Maternal age and fetal loss: population based register linkage study
Anne-Marie Nybo Andersen, Jan Wohlfahrt, Peter Christens, Jorn Olsen, Mads Melbys
RMJ Volume 320 24 JUNE 2000
7. Age and miscarriage following IVF
Outcomes of 124,351 pregnancies following IVF
Sunkara et al., ASRM 2012
Age
1 ≤34 years
2 35 – 37 years
3 38 – 39 years
4 40 – 42 years
5 43 – 44 years
6 ≥45 years
8. Miscarriage following ART
• Outcome of 62,228 clinical pregnancies following ART
US between 1996 – 1998
• Spontaneous miscarriage rates following ART
compared with miscarriage rates from a population-
based survey of US women aged 15 – 44 years
Spontaneous Abortion Among Pregnancies Conceived Using Assisted Reproductive
Technology in the United States
Laura A. Schieve, PhD, Lilith Tatham, DVM, MPH, Herbert B. Peterson, MD, MPH, James Toner, MD, Phd and Gary Jeng, PhD
Vol. 101, NO.5, PART 1, MAY 2003
11. Cause of miscarriage
• Cytogenetic analysis of products of conception
(POC) following spontaneous miscarriage
• 133 POC following ART and 144 from infertile
couple following natural conception
Chromosomal abnormalities in miscarriages after different assisted
reproduction procedures
D. Bettio, A. Venci, P.E. Levi Setti
Placenta, 29 (2008) S126-S128
13. Maternal age and aneuploidy
• 258 blastocysts from 51 cycles analysed after biopsy
and microarray
• 43.4% euploid and 56.6% aneuploid embryos
• Aneuploid rates significantly higher in older women
– 44.2% (<35 years); 43.9% (35-37years); 56.4% (38-40
years); 82% (≥41 years)
DNA Microarray reveals that high proportions of human blastocysts from women of
advanced maternal age are aneuploid and mosaic.
Jianqiao Liu, Weihua Wang, Xiaofang Sun, Lian Liu, Man Li, Craig Witz, Dan Williams, Jason Griffith, Josh Skorupski, Gus Haddad and
Jimmy Gill
BIOLOGY OF REPRODUCTION (2012) 87 (6):148, 1-9
14. Maternal age and aneuploidy
Retrospective study of 353 miscarriages karyotyped and grouped
according to number of miscarriages and maternal age
The effect of maternal age on chromosomalanomaly rate and spectrum in recurrent
miscarriage
Maribel Grande, Antoni Borrel, Raul Garcia-Posada, Virginia Borobio, Myriam Munoz, Montserrat Creus, Anna
Soler, Aurora Sanchez, and Juan Balash
Human Reproduction, Vol. 27, No. 10 pp.3109-3117, 2012
15. Mastenbroek et al., Hum Reprod Update 2011
LBR significantly lower in PGS group (18%) compared to
controls (26%)
Role of PGS?
16. CCS for embryo assessment
Molecular Human Reproduction Vol.14, No.12 pp. 703-710, 2008
Advance Access publication on November 28, 2008
New Research Horizon
Use of Comprehensive chromosomal screening for embryo assessment: microarrays
and CGH
Dagan Wells, Samer Alfarawati and Elpida Fragouli
17. CCS in advanced age
• Study group (n=30) frozen blastocyst transfer with
euploid embryos tested by CCS
• Control group (n=30) fresh blastocyst transfer;
embryos selected based on morphology
– IR 40.9% vs 60.8% (p<0.05)
– Miscarriage rate 0% vs 20% (p<0.01)
Comprehensive chromosome screening (CCS) with vitrification results in improved
clinical outcome in women > 35 years : randomized control trial
W.B. Schoolcraft, E. Surrey, D. Minjarez, R.L. Gustofsonm R.T. Scott, Jr., M.G. Katz-Jaffe
18. Conclusion
Poor oocyte quality cause of reduced
implantation
Chromosomal anomalies cause for increased
miscarriages
Role of CCS using CGH need to be evaluated in
larger RCTs
