IVF started to develop fast with the aim of maximizing pregnancy rates per cycle Higher number of oocytes and thus more embryos Use of unphysiological high doses of gonadotropins Time consuming protocols Higher costs Patient discomfort Higher risk of OHSS Very high risk of multiple gestation

1. 1

2. Influence ICOS on oocyte and embryo quality
Less is more…
Individualization of Ovarian stimulation

3. Why ovarian stimulation ?
Retrieve multiple oocytes for IVF procedure
Have multiple embryos available to choose from
Compensate for suboptimal fertilisation and
implantation
Have access embryos for cryostorage
Improve IVF outcomes

4. IVF started to develop fast with the aim of
maximizing pregnancy rates per cycle
Higher number of oocytes
and thus more embryos
• Use of unphysiological high
doses of gonadotropins
• Time consuming protocols
• Higher costs
• Patient discomfort
• Higher risk of OHSS
• Very high risk of multiple
gestation
Rapid progression of
protocols and technology

5. Sequela of ovarian
stimulation for IVF
(Oehninger & Hodgen.
Baill Clin Obstet Gyecol 1990)
Consequences for
luteal phase endocrinology
Endometrial receptivity Embryo
quality/aneuploidy

6. 74% of failed IVF = failed implantation
started oocyte embryo pregnancy ongoing
cycle retrieval transfer pregn
92%
81%
27% (37% cum)
21% (27% cum)
Total 16.898 started cycle
48% ICSI
Cum = fresh+froozen ET
91% singleton pregnancies
IVF results, The Netherlands, 2010

7. Relevant studies in mice
Superovulation in mice causes
Reduced oocyte quality
Reduced embryo quality
Delayed pre-implantation embryo development
Reduced implantation
Fetal growth retardation
Abnormal methylation of imprinted loci
Negative impacts on oviductal and uterine milieu
Laprise, Mol Reprod & Dev 2009

8. Objective
Chromosome error rate from oocytes
generated for ICSI in women < 35 yrs
Patients N=933 couples undergoing ICSI
Methods Polar body testing chromosomes 13,16,
18, 21, 22
conclusions
High yield of oocytes is associated with increased
chromosome error rate
Results; chromosome error rate in relation to Oocyte No.
Oocyte # 1-5 6-10 > 10
Chromosome
error rate
23+5% 35+4% 51+6%

9. Objective Study effects of FSH on
aneuploidy in IVM oocytes
Patients Male factor infertility, ICSI
(86 cycles, 252 oocytes)
Interventions FSH; 0.5; 5.5; 22; 100; 2000 ng/ml
Polar body biopsy; chrom 13, 16, 18, 21, 22
Results Aneuploidy rate;
27, 23, 37, 47, and 63%, respectively
conclusion High FSH concentrations during IVM
sign. increases first meiotic division error
Fertil Steril 2010

10. GnRH agonist (long prt)
rFSH (225 IU/d)
CD 2 5 foll > 14 mm
GnRH antag
rFSH (150 IU)
PGS: 2 blastomeres
10 chromosomes
1, 7, 15, X, and Y
13, 16, 18, 21, 22
111 Patients
528 fertilized oocytes
302 embryos FISHed
RCT

11. Correlation between oocyte number
and embryo aneuploidy Baart, HR 2007

12. 4033N =
%abnormal
embryosdiagnosed
100%
80%
60%
40%
20%
0%
Conventional
Mild
Embryo aneuploidy for
mild vs conventional stimulation
P = 0.016

13. Ovarian hyperstimulation for IVF
- the bigger picture
Ovarian
stimulation
cost Burden of
treatment
Drop out
(cum
outcomes)
monitoring
complex
Complications
(OHSS)
contribute to success?
Drop outAccess to
treatment

14. This magic wheel had to slow down

15. Definition of success in IVF started shifting from
pregnancy rate per cycle towards achieving
healthy singleton child per started course of
treatment.
For achieving this aim the first
change had to be in the
stimulation protocols with the
aim of:
•Less oocytes
•less pain /stress
•less cost
•Less complications
•Obtaining a good oocyte /
embryo/ implantation rate
Further progression of
technology aimed at
minimizing complication
rate yet maintaining
optimal pregnancy rates

16. How to balance
too much vs too little?
Context ovarian stimulation
Impact ovarian stimulation on oocyte / embryo
Wider implications

17. HR 2012
Iive birth in relation to oocyte yield

18. Optimal number of oocytes for IVF
Patient
perspective
Society
perspective
Child
perspective

19. conventional Individualization

21. Proposed Models for “Individualization”
Nelson et al.
(2009), Yates
et al.(2011)

22. Proposed Model for “Individualization”
AGE & AMH,FSH
AGE & AFC,FSH
Dr Dhorepatil 22

23. Starting Dose..key to response?
• How much FSH depends on the threshold of
the pt..individual varies
• This could be stratigies depends on Age, BMI,
AFC, AMH, type of Infertility , Previous
response
23

24. IGD Score

25. AIMS AND OBJECTIVES
• To retrospectively analyse the patients who have
undergone IVF cycles with fixed and individualised
gonadotropin dose depending on IGD score.
• To compare the outcome of COH in IVF cycles No of
follicles & no of oocytes with fixed and individualised
gonadotropin dose depending on IGD score.

26. • This retrospectively observational study was carried
out at Ssmile IVF Centre and Pune fertility Centre
under the guidance of HOD, Dr. Bharati Dhorepatil by
Dr Nikita Singh.
• The analysis of database was done which had clinical
and lab information regarding IVF treatment cycles.
• The data was collected and recorded in the
registered database of the fertility Centers.

27. Flow chart of study design
Evaluation of the individual
Fixed dose
FSH 225 from D-2
Antagonist from D-6
Trigger- HCG 5000 IU (≥3
follicles of ≥16 mm)
OPU
Oocyte Evaluation
IGD
FSH as per IGD score
from D-2
Antagonist when atleast
1 follicle ≥12-14 mm
Trigger- rHCG 250
(≥3 follicles of ≥16 mm)
OPU
Group 1 Group 2

29. Table No. 8: In the current study, group 1 patients were three years
younger as compared with group 2. Mean age of group 1 was 28.05
years as compared to 31.25 years of group 2. This was statistically
significant (P value 0.05).

36. Conclusion of the study
• Individualization score seems to be effective in
getting optimum oocytes and negating sever OHSS
• Although MII oocytes are more in no with fixed
protocol, IGD gives better fertilization,embryo quality
and implantation

37. Our other Experience
• Lotus II Trial.. Intrim Observations
• 45 pts recruited
• Mild stimulation with antagonist and HCG trigger
targetting only 5 to 6 follicles
• Two embryos transfer
• Luteal support only Gel Vs Tab..Randomised
• 51% Pregnancy rate..clinical, Viable
• 55% implantaion rate
• One ectopic pregancy

38. • Adopt protocols to fit the need of an individual
patient as per different parameters
• Respect a woman’s desire of minimal stimulation
• ICOS for patients with oncologic issues with
urgent need for oocyte or embryo cryo
preservation.
• Pro-thrombotic conditions or oestrogen
dependent cancers at risk with high oestrogen
levels during COS
• Individualization is the need of hour
Summary

39. Tip… successful ovulation Induction
• You are not doing Ovarian stimulation, but
• You are preparing egg from given ovary to get
pregnancy out of it..
39

40. • There is no golden standards, guidelines or
protocol.
• As there is no golden rule, induction of ovulation
depends largely on the doctors experience and
patients merits.
• Think twice before starting induction, and avoid the
routine.
40

41. OVULATION INDUCTION
IS NOT ONLY A SCIENCE
BUT ALSO AN ART of Endocrinology

42. 42