A Controlled Clinical Study

1. 1
Assisted Reproductive Technology InAssisted Reproductive Technology In
Women Over 40yearsWomen Over 40years
A Controlled Clinical
Study

2. 2
 M.WALAA ELDEEB MS
 HISHAM EL ENANY MD
 OSAMA SHAWKY MD
 SHERIF S. SAID MS
 GHADA HARFOUSH MS
 SHERIF EL SHAMY

3. 3
Introduction
Numerous demographic studies suggest a
consistent decline in fecundity with
increasing age.
Szamatowicz & Grochowski , 2002

4. 4
 Age has a significantly
negative
effect on
ovarian
stimulation.
 Short protocol for
IVF
is the traditionally
used one
in women
over 40 ys.

5. 5
Objective
There is lack of
evidence to support
the use of short
protocol in
advanced female
age.

6. 6
The aim is to
compare results of
short vs long
protocols for
IVF/ICSI in women
over 40 ys.

7. 7
Design
 Multicenter controlled trial.
 Eight centers allover Egypt participated in this
study.
 The Egyptian IVF-ET center, Integrated Fertility
center (Cairo & Alexandria), Miami Fertility
center, Mansoura Fertility center,Elmadina
Infertility center…..etc

8. 8
Inclusion criteria
 All women had FSH less than 20 before start
of treatment.
 No functional azospermia.
 No submucous fibroid.
 First trial of ICSI (or previous trial with good
response)

9. 9
Participants
 A total of 531 women ranging between 40-
47ys were enrolled in this study ;
– 285 women received long protocol
– while 246 women received short protocol.
 Standard ICSI program was done for all
cases.

10. 10
Results
 Regarding all women, clinical pregnancy was
achieved in 101 women (19%) and miscarriage rate
was (32%) mainly in the first eight weeks.
 No pregnancies were
achieved above 43
years.

11. 11
Variables Long short P value
Age (Ys) 42 ± 1.6 43 ± 0.4 N.S
Duration
(Ys)
11.3 ± 4.5 10.2 ± 3.1 N.S
FSH
(mIU/mL)
12.4 ± 2.6 11.8 ± 1.9 N.S
HMG (IU) 5730±1930 4260±585 0.030.03

12. 12
Variable Long short P value
E2 2100 ± 1230 1400 ± 680 0.023
Oocytes 9.4 ±3.2 5.1 ± 2.4 0.04
Fertilization
rate
62% 43% 0.03
Embryos 6 ± 2.4 3 ± 1.3 0.01

13. 13
Variable long short P value
ET 4.3 ± 1.8 2.2 ± 1.5 0.03
Pregnancy
rate
26.6 % 10.2% <0.001*
Miscarriage
rate
32% 29% N.S
OHSS 0 0

14. 14
Other outcomes
 Cost of drugs : were significantly reduced with the
short protocol (P =0.031*)
 Multiple pregnancy : only one case in the long
protocol.
 Cancellation rate :
was significantly higher for
Long protocol
19.5% vs 11%
for Short protocol (P<0.05*)

15. 15
Discussion
 Fertility declines gradually from the age of 30
years, but declines dramatically after 40
years. (Lesser , 1999)
 The question is it
biological aging or
chronological aging.

16. 16
Decline may be due to:
 Decrease in ovarian reserve with advancing
age.
 Decrease in the quality of oocytes as
indicated by the increased incidence of
oocyte aneuploidy.
 A decrease in endometrial receptivity
(Swanton & Child , 2005)

17. 17
Protocols of stimulation
 The long protocol is the
most widely used
protocol because it is
the best for
suppression of
endogenous LH levels
in normogonadotropic
patients.

18. 18
 Traditionally, the short
protocol is used for
older women because
of the well-known 'flare-
up phenomenon'.
Sbracia et al, 2005

19. 19
Why our study is unique ????
 Very few studies compared long vs short
protocols in advanced women age.
 The results are interesting and needs to
be confirmed by other investigators.

20. 20
How to explain
The objective of controlled ovarian
hyperstimulation (COH) is to ensure the
adequate development of early antral
follicles to increase the number of viable
oocytes

21. 21
One of the key points of such a procedure is the
achievement of adequate synchronization of
follicular growth so that ovulation can be
triggered when most follicles have reached
concomitant maturation.

22. 22
However, to obtain a good follicular coordination
during COH, the nature selection of follicles
observed during the early follicular phase should
be overcome.

23. 23
Explanation
 Our participants were normogonadotropic.
 GnRH agonist resulted in better follicular
synchronization and more or less
symmetrical oocyte development.
 Ending into higher number of oocytes that
allowed better selection of embryos to be
transferred.

24. 24
Conclusion
This multicenter study shows that long
protocol of GnRH agonist was better
than short protocol in women with age
of 40 or above.

25. 25