1. CV - Dr. Suresh Kattera, Singapore
Director, Asia-Pacific Institute of Embryology-offers MSc in clinical embryology & pre-implantation genetics & 2 weeks training in embryology
Scientific Director, Pearl-Singapore Fertility Centre & Research Institute
More than 25 years of experience and has several achievements in the field of IVF;
First in the world to show rescue ICSI can be performed after 6 hours (Human Reproduction Vol.18, 2003).
Reported the world’s first birth after enucleation of tripronuclear zygotes (removal of extra male pronucleus) (Human Reproduction Vol.18, 2003)
First to modify slow freezing method to show frozen embryos have higher success than fresh embryos (Fertil Steril, 2005; 84, 2005).
Achieved first vitrification live birth in Singapore and in Asia in 2001 (IJS 91; 2006)
Was a team member of the first ever ovarian tissue transplant performed in Singapore and probably in Asia (2011)
Showed for the first time 4 types of pronuclear orientation in the zygotes (Human Reproduction Vol.19, 2004)
Scientific Director of Gleneagles Hospital IVF centre, Singapore -top centre in terms of success among the 10 centers from 1997-August 2009 (Ministry of Health, Singapore Publication 2003)
Manuscript reviewer for various journals including Human Reproduction, Reproductive Biology & Endocrinology.
Hold IP for designing a device (SEP-D) to process semen

2. Blastocyst transfer for all-Are we there yet?
Dr. Suresh Kattera
Singapore
Director, Asia Pacific Institute of Embryology
Scientific Director, Pearl Singapore Fertility Centre & Research Institute
September 22, 2017
AFRH, Abuja, Nigeria

3. Singleton healthy baby
Introduction
Objective
Singleton healthy baby
Selection of viable embryo
Identification of synchronized endometrium
First report of blastocyst pregnancy - Cohen et al 1985
Constant increase in blastocyst stage transfer

4. Indications and Criteria
To avoid multiple pregnancies
Improve the pregnancy and live birth rates
Repeated failed cases
More than four-five 8c embryos on day 3

5. Cleavage stage vs Blastocyst stage
Questions?
When and how many should we transfer?
Should it be on day 2 or day 3 or day 5?
Is there a difference between them in terms of success?
Read in between the lines?
Cleavage stage vs Blastocyst stage

6. Differences between different days of transfer (e. g
Differences between different days of transfer (e.g. 100 oocyte retrieval cycles)
Day 2
Day 3
Day 5
Embryos available for transfer
All
approx. 70
Embryos available for freezing
50-60%
30%
Pregnancy rates/ET cycle
40-45%
50-60% (70 /ET cycles)
40-45%(100/started cycle)
Multiple pregnancy
<15%
>20% ??

7. Reasons for extended culture?
Implantation and pregnancy not optimum and didn’t correspond to morphology
Did PN morphology help?
Tesarik &Greko(1999) modified grading
Nucleoli-size,number and distribution
Single observation scoring
Strong association-implantation & equality

8. New classification based on zygote morphology & early cleavage status
kattera and Chen (Fertility and Sterility 2006)
Nucleoli size, number and distribution
Large 1-12
Medium less female
Small/pinpoint

9.                            
Kattera and Chen (Hum.Reprod 2005)
new classification of zygotes based on PN orientation-PN1, PN2, PN3 and PN4 in relation to polarity

10. Other reasons?
Minimizing exposure of embryos to hyper stimulated environment
Synchronizing embryo and environment
Optimal embryo selection with highest implantation potential
Reducing uterine contractions

11. Reality check Not all embryos become blastocysts
About 50% on an average in sequential medium
Some do not expand fully
Some do not have enough ICM
Some look unhealthy
Why?

12. Culture system?
In vitro Culture system not optimum? Micro-environment/macro-environment
It cannot provide all the nutrient requirements for some of the embryos
Some of these embryos develop further in vivo but not in vitro
Gamete quality

13. Ray of hope? Single step medium
Main purpose-avoid ammonia accumulation
Other benefits- accelerated growth

14. Comparison of sequential and single step medium (Surelife, Singapore)
Sequential media
Single Step media
Fertilization rate
>70%
Early cleavage (day 1)
Yes
Day 2-embryo stage
4-5 cell
8c (20-30%)
Blastulation rate
About 50%
About 83%

15. Reasons?
Improved culture media- nutritional requirements different for different embryos
Ideal culture media
100% blastocysts in vitro?

16. Concerns of blastocyst transfer
Pre-term birth
Two separate meta-analyses have confirmed- higher relative risk for pre-term compared to cleavage stage embryos (Dar et al.,2014; Maheshwari and Bhattacharya, 2013; Maheshwari et al.,2013)
Risk of monozygous twins
Existing data suggest an increased chance of monozygotic twins (Chang et al., 2009; Luke et al., 2014)

17. Congenital anomalies
A recent meta-analysis (Dar et al., 2014)-congenital anomalies were significantly higher for babies born after embryo transfer at blastocyst stage compared with those born after embryo transfer at cleavage stage
Epigenetic changes
Effect of culture medium and culture environment on epigenetic reprogramming and development

18. Arguments in favour of Cleavage stage embryos transfer
Unaltered sex ratio and reduced congenital anomalies
Decreased pre-term delivery
Decreased monozygotic twins
Increased cumulative live birth rates

19. Strategies?
Previous criteria > 4-5 embryos with 8C considering 50-60% blastulation rate on an average
Single step medium and blastulation rate 83% is encouraging-Should we attempt blastocyst transfer for all?
Re-adjustment- any patient with at least 2x8c embryos in single step medium
Are we able to achieve 100% blastulation? -gamete quality major determinant

20. Strategies?
Transfer either on day 3 or day 5- decide on a case by case basis by the embryologist
Consider Laboratory culture conditions -Yes
Freeze all and culture them to blastocyst stage and vitrify supernumerary embryos?-Yes
Consider safety issues-Yes

21. Conclusions
Improve culture medium/culture conditions to achieve maximum blastulation rate
RCTs to Compare sequential and Single step medium- various outcomes including epigenetic reprogramming
More RCT on safety of blastocyst transfers outcomes as compared to cleavage stages required
Consider 100% FETs
Each Centre should have its own policies regarding the day of transfer

22. Thank you…