ART: Factors affecting success

1. Benha University Hospital, Egypt
Email:elnashar53@hotmail.com
Aboubakr Elnashar

2. •IVF specialist
1. Identification
of the successful
techniques
2. Valid
comparison
between the
results of
different centers
•General
gynecologist who
make most of
referrals.
1. Treatment of the
factors decreasing
success before
ART
2. Proper
counseling
regarding the
factors that can not
•Infertile
couple who
should be
involved in
decision
making.
Importance of definition of these factors
Aboubakr Elnashar

3. Aboubakr Elnashar

4. ART success rates: are expressed in several ways
The 2 most common
1. Pregnancy rate (PR)
2. live birth: more relevant.
Pregnancy or live birth can be calculated as a
percentage of
cycle starts,
retrievals, or
transfers.
In Egypt (2000): PR/retrieval:
28.9% for ICSI (The Egyptian IVF
registry; Mansour,2003)
Aboubakr Elnashar

5. Couple
1. Age
2. Ovarian reserve
3. Number of
previous treatment
cycles
4. Duration of
infertility
5. Type of infertility
6. Cause of infertility
7. Body weight
8. Smoking, alcohol,
caffeine
consumption
Technique
I. Stimulation protocol
II. Oocyte retrieval
III. Laboratory
IV. Embryo transfer
V. Luteal phase support
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6. Aboubakr Elnashar

7. I. Age
A woman’ ability to become pregnant declines with age
both naturally & with treatment (Templeton et al, 1996).
Age (years) Live birth/
treatment cycle (%)
23-35
36-38
39
40 or older
>20
15
10
6Aboubakr Elnashar

8. II. Ovarian reserve
Women with decreased ovarian reserve respond
poorly to COH & have poor clinical outcome in
IVF (Sharif et al,1998).
• Ovarian reserve:
Basal FSH: >15
Inhibin B: <45
Ovarian volume
Antral follicle count: <5
Anti-mullerian hormone: <1ng/ml
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9. III. Number of previous treatment cycles
The delivery rate for cycles:
1: 27%
2: 27.4%
3: 23%
4: 16%
>4: 15% (Meldrum et al,1998)
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10. IV. Type of infertility
ART is more effective in women who have previously
been pregnant &/or had live birth (NICE,2004)
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11. V. Duration of infertility
A significant decrease in PR with increasing
duration of infertility (HEFA data base,1996).
1-3Y: 15%
4-6Y: 14%
7-9Y: 13%
10-12Y: 12%
> 12Y: 9%
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12. VI. Cause of infertility
Live birth rates were
27% for male factor,
26% for endometriosis,
25% for tubal factor,
25% for unexplained infertility
23% for ovulatory dysfunction (Templeton et al,
1996).
In Egypt (2000):
Female factor represented 16.6% of the cycles
Male factor represented 56% of the cycles (The
Egyptian IVF registry; Mansour,2003)Aboubakr Elnashar

13. Hydrosalpinx:
Hydrosalpinx had a negative effect on PR, IR,
early pregnancy loss & live delivery rate.
{The fluid of hydrosalpinx may constitute a
mechanical barrier to implantation by causing
the embryo to float
Hydrosalpinx fluid is deficient to support the
developing embryo
Hydrosalpinx is toxic to the developing embryo}.
Salpingectomy resulted in improvement of
outcomes (NICE, 2004)
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14. Male factor:
In IVF: poor success rates due to poor fertilization rate
In ICSI: dramatic improvement in the outcome.
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15. Endometriosis:
• Minimal & mild: No effect (Vrtovec et al,2000)
• Moderate & severe: The fertilization rate, PR per
transfer, & birth rates were significantly lower (Azim
et al,1999; Garrido et al, 2000).
On other hand, HFEA database (2000)
did not show lower PR in endometriosis, but it did not
take into account the stage of endometriosis.
•
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16. Fibroid:
Fibroids not causing deformity of the uterine cavity &
<7 cm did not affect the implantation or miscarriage
rate in ART (Ramzy et al,1998).
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17. VII. Body weight
BMI should ideally be in the range 19-30 before
commencing ART. The BMI outside this range is
likely to reduce the success of ART(NICE,2004).
On other hand Wass et al (1997) revealed that BMI has
no effect on PR but that the android body fat
distribution
WHR >0.8: PR is 16%
0.7-0.79: PR is 30%.
{Excessive androgen levels have a negative effect on
oocyte development resulting in poor quality
embryo}
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18. VIII. Smoking, alcohol, Caffeine
consumption
• PR amongst smokers (maternal or
paternal)were significantly lower than non-
smokers after IVF.(14% Vs 21%) (Feichtinger
et al,1997)
• Consumption of more than one unit (12 g) of
alcohol per day reduces the effectiveness of
ART, including IVF (NICE,2004)
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19. • Caffeine consumption (over 2-50 mg/d Vs 0-2
mg/d; 100 mg caffeine in one cup of coffee)
during lifetime & during the week of initial visit
for infertility has adverse effects on the
success rates of ART including IVF (Kohen et
al, 2002).
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20. Aboubakr Elnashar

21. The success rate of IVF & ICSI vary from one
center to another ranging from 4% to 36% per
cycle started, in UK (HEFA,2000).
1. Some clinics are better than the others:
in their clinical & embryology practices.
2. Patient selection:
Some centers decline to treat patients with
poor prognostic factors
3. Success rates are reported differently.
No reporting of cancelled cycles.
Success rate per number of cycles started,
oocyte retrieval, embryo transfer.
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22. I. Ovarian Stimulation
COH leads to the creation of numerous embryos, which
could be available for transfer or cryopreservation,
thus increasing the chance of pregnancy (Wang et
al,1994).
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23. 1. GnRH agonist Vs HMG:
• The use of GnRH agonist in down regulation protocols
improves the IVF outcome
• Clinical PR increases compared to the use of HMG alone
(Hughes et al, 1992).
{Allow many follicles to reach maturity thereby increasing the
number of oocytes collected & reducing the cancellation rate.
Prevent premature LH surge & consequently spontaneous
ovulation, making cycle monitoring much easier} (Wang et
al,1994).
Spontaneous abortion was similar.
• However, GnRHa was associated with a slight, but
insignificant increase in the incidence of OHSS & multiple
pregnancy
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24. 2. Long Vs short protocols:
Long stimulation protocols are superior to short &
ultrashort protocols in terms of clinical pregnancies
(Daya, Cochrane library, 2002).
3. GnRH agonist Vs antagonist:
The clinical PR was significantly lower in the antagonist
group (Al-Inany & Aboulghar, Cochrane library,
2002)
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25. 4. Urinary FSH Vs HMG:
CPR was higher when uFSH was used compared to
HMG (Daya, Cochrane library, 2002).
5. Rec FSH Vs uFSH:
No statistically significant difference in PR/started cycle
between rec FSH & uFSH (Al-Inany et al, 2003)
Aboubakr Elnashar

26. II. Oocyte retrieval
1. Vaginal disinfection with povidine iodine:
PR was significantly higher in the normal saline group
(17.2% Vs 30.3%)
2. The number of oocytes retrieved:
< 4 oocytes: reduced fertilization, CPR, & live birth
(Victory et al, 2004).
>4 oocytes: Similar chances of success for all
Aboubakr Elnashar

27. III. Laboratory
1. ICSI Vs IVF:
In couples with borderline semen, ICSI results in higher
fertilization rates (van Rumsteke et al, Cochrane library,
2002)
In couples with normal semen, ICSI results in higher
fertilization rates per oocyte injected but not per
oocyte retrieved compared to conventional IVF.
Aboubakr Elnashar

28. Tubal factor infertility: IVF should be the initial
treatment of choice (Aboulghar et al,1996; Bukulmez et
al,2000).
{No significant difference in PR or take-home baby}.
Unexplained infertility: ICSI should be the first option
(Sertac et al,2000).
{Complete fertilization failure was higher in
conventional IVF (34.3%) than ICSI (10.3%)} (Jaroudi
et al,2003).
Aboubakr Elnashar

29. 2. Co-culture & group culture:
The value of Co- culture in improving PR has not been
established (Veiga et al,1999)
RCTs failed to prove that culturing the embryos in
groups improve the CPR (Spyropoulou et al,1999).
3. Embryo selection:
The clinical value of embryo selection based on scoring
systems has not been established by RCTs
(Sallam,2003).
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30. 4. Assisted hatching:
The results of RCTs have been controversial & there is a
need for a large RCT (Sallam, 2003).
5. Embryo cryopreservation:
The main aim is to increase the chances of achieving a
live birth from a single COH cycle. The average CPR
in frozen embryo replacement cycles are 15%
(HEFA,2000).
Cryopreservation increased the PR by 11% (Wang et al,
1994)
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31. IV. Embryo transfer
1. Trial (dummy, mock) transfer:
Clinical P & IR are significantly increased
(Mansour et al, 1990).
Trial ET:
determines the most suitable catheter &
avoids unexpected difficult & failed ET.
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32. 2. The best day for embryo transfer:
Day 2 Vs day 3:
Although an increase in CPR with D3 ET, there is no
sufficient good quality evidence to suggest an improvement
in live birth
(Oatway et al, 2004, Chocrane library).
Day 2 or 3 (early) Vs day 5 or 6 (late):
Day 5 ET has no advantages over day 3 (Sallam et al, 2003;
meta-analysis).
Little difference in the major outcome parameters between
early ET & blastocyst culture
(Blake et al, 2004, Chocrane library).
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33. 3. Type of ET catheter:
PR was significantly higher in soft catheter
(van Weering,2002).
PR was increased by 50% when the soft double lumen
catheter rather than the single lumen catheter was used
(McDonald & Norman ,2002).
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34. 4. Ultrasound-guided ET:
is associated with an increase in the CPR & IR
(Salam & Saad-eldin ,2002; Buckett 2003 ,meta-analysis)
Value of UGET:
- confirm that the embryos are properly deposited
- to follow the embryo-associated air bubble
- increases the frequency of easy ET.
- decrease cervical & uterine trauma
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35. 5. Site of embryo deposition
IR was significantly higher when the embryos were
deposited 2 cm below the uterine fundus (Coroleu et al
,2002).
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36. 6. Number of embryo transferred
• To balance the chance of a live birth & the risk
of multiple pregnancy, no more than 2 embryos
should be transferred (NICE, 2004; HEFA,
2000)
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37. Age (ys) Favorable
conditions
No favorable
conditions
< 35
35-37
38-40
> 40
1
2
3
5
2
3
4
5
• ASRM (2004)
Most favorable conditions.
1. The first cycle of IVF
2. Previous success of IVF
3. Good Quality embryos
4. Excess of embryos of sufficient quality to warrant
cryopreservation
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38. V. Luteal phase support
1. IM Vs oral:
IM P conferred the most benefit compared with oral P
(meta-analysis, Prittis & Atwood, 2002)
2. Vaginal Vs oral:
• The C & OPR were significantly lower with the oral
formulation (Pouly et al, 1996; Frieder et al, 1999, Sucedo
et al, 2000).
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39. 3. Addition of E To P:
1. No advantage
(Lewin et al, 1994; Smitz et al,1993;Tay & Lenton,
2003; Rashidi et al,2004).
2. Beneficial effect on IR & PR (Farhi et al,2000;
Gorkemli et al,2003).
3. Beneficial effect on PR in patients with
profound E2 decline (E2 on day of HCG/ E2 of ET
>50%) (Lakkis et al,2002; Gleicher et al,2000).
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40. 4. Progesterone plus Prednisolone & Low dose aspirin
No benefit on PR , but it may reduce the rate of
spontaneous pregnancy loss (Mollo et al,2003)
Progesterone plus ascorbic acid
No benefit (Griesinger et al, 2002)
Aboubakr Elnashar

41. Benha University Hospital, Egypt
Email: elnashar53@hotmail.com
Aboubakr Elnashar