ART: Factors affecting success: ABOUBAKR ELNASHAR

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 be treated
e.g. age
•Infertile
couple who
should be
involved in
decision making.
Importance of definition of these factors
Aboubakr Elnashar

3. Aboubakr Elnashar

4. ART success rates
Expressed in several ways
1. PR
2. LBR: more relevant.
PR or LBR can be calculated as a percentage of
cycle starts,
retrievals, or
transfers.
Aboubakr Elnashar

5. Mansour et al, 2014
The Egyptian IVF registry report:
ART in Egypt 2005
 Twins: 23.7%
Triplets: 2.6%
OHSS: 1.8%
BR/ETPR/ ET
26.8%35%Fresh
18.5%25.6%Frozen
Aboubakr Elnashar

6. A. Couple
1. Age
2. Ovarian reserve
3. Number of previous
tt cycles
4. Previous pregnancy
and live birth
5. Duration of infertility
6. Cause of infertility
7. Body weight
8. Life style
B. Technique
I. Stimulation protocol
II. Oocyte retrieval
III. Laboratory
IV. Embryo transfer
V. Luteal phase support
Factors
A. Center
overall success rate of
centre
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7. A. IVF CENTER Factors
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8.  UK: (HFEA 2002)
LBR/cycle: 22%
varies between different clinics: 10% to 46%.
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.
Aboubakr Elnashar

9. 4. The size of the clinic
In general, large IVF centers have higher success
rates than small clinics. However, some small clinics
have very good results.
LBR/cycle
UK USA
Information source HFEA 1997 Report SART 2002 Report
Large centres 15.7% 34.3%
Small centres 12.6% 30.0%
Aboubakr Elnashar

10. 5. Skill and experience of the team including,
doctors, nurses and embryologists
Even in the same clinic with the same clinical
protocol and a single embryology laboratory, IVF
outcome varies between different doctors.
(Karandi et al, 1999)
CPR vary between 8.3 to 40% between different
physicians.
IVF outcome varies between different
embryologists
Aboubakr Elnashar

11. Aboubakr Elnashar

12. I. Age
 LBR: decreases significantly from the age 35 y
41 and over: 7.1% /cycle
 The older the woman:
higher the chance of cancellation
lower the chance of success
higher chance of miscarriage
chromosomal abnormalities.
 A woman’ ability to become pregnant declines with
age both naturally & with tt
(Templeton et al, 1996).
Aboubakr Elnashar

13. Aboubakr Elnashar

14. Age
group
Less than
35
35-37 38-40 41-42
Pregnancy 43.1% 35.7% 26.8% 17.6%
Live birth 37.3% 29.5% 19.7% 10.6%
Data adapted from SART report 2005
Aboubakr Elnashar

15. Age 2004 2005 2012
Less than 35 36.9% 37% 40.7%
35-37 29.3% 29% 31.3%
38-40 19.5% 20% 22,2%
40-42 10.7% 11% 11.8%
43-44 4.4% 3.6% 3.9%
Over 44 <1% 0.7%
LBR/ cycle: SART reports: 2004,2005 and 2012
Aboubakr Elnashar

16. Age 2005 2006 2007
Less than 35 29.6% 31% 32.3%
35-37 23.6% 26.4% 27.7%
38-39 18.2% 18.6% 19.2%
40-42 10% 11.1% 11.9%
43-44 3.2% 4.6% 3.4%
Over 44 0.8% 4.0% 3.1%
HFEA patient reports 2005, 2006 and 2009
Aboubakr Elnashar

17. 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
> 12 IU/L
 AFC: <5
 AMH: <1ng/ml
 FSH/LH: > 3
Aboubakr Elnashar

18. Predictors of ovarian response to Gnt stimulation in
IVF: (NICE, 2013)
High responseLow response
16 or more4 or lessTotal AFC
3.5 or more
25
0.8 or less
5.5
AMH
ng/ml
pmol/l
Conversion ratio:7
4 or less8.9 or moreFSH IU/L
Aboubakr Elnashar

19. III. Number of previous tt cycles
 The delivery rate for cycles:
1: 27%
2: 27.4%
3: 23%
4: 16%
>4: 15% (Meldrum et al,1998)
 Chance of a live birth following IVF tt falls as the
number of unsuccessful cycles increases.
 LBR is highest in 1st cycle (17.4%)
and drop to 14.4% by 5th cycle (HFEA Report 1999).
 Although cycles 6-8 appear to give a reasonable
chance of success, few patients persevere that
long.
Aboubakr Elnashar

20. Age
group
less than
35
35-37 38-40 41-42
43 or
over
No
previous
tts
33.9% 27.3% 18.7% 11.2% 3.8%
Had
previous
tt cycles
28.5% 23.7% 16.1% 8.7% 3.7%
Data adapted from SART report 2002
Aboubakr Elnashar

21. IV. Previous pregnancy and live birth
IVF is more effective in women who have
previously been pregnant &/or had live birth
(NICE,2004)
Previous pregnancy or live birth rate LBR/ET
Woman has never been pregnant 12.5%
Woman conceived naturally but no live birth 13.7%
Woman conceived naturally and has a live birth 15.3%
Woman conceived by IVF but no live birth 16.6%
Woman conceived by IVF and has a live birth 23.2%
HFEA Report 1998 Aboubakr Elnashar

22. Age group
Less than
35
35-37 38-40 41-42
No
previous
live births
36.4% 28.6% 18.8% 9.9%
One or
more live
births
40.3% 31.4% 21.6% 11.9%
SART report 2005.
Aboubakr Elnashar

23. 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%
Aboubakr Elnashar

24. VI. Cause of infertility
 LBR:
27% for male factor,
26% for endometriosis,
25% for tubal factor,
25% for unexplained infertility
23% for ovulatory dysfunction
(Templeton et al, 1996).
Aboubakr Elnashar

25. Cause of infertility LBR/ET
Tubal 13.3%
Endometriosis 15.0%
Unexplained 15.9%
Male 19.6%
Aboubakr Elnashar

26.  Hydrosalpinx:
 10 to 30% of couples presenting with infertility due to
tubal factor.
 negative effect on PR, IR, early pregnancy loss &
LBR.
LBR are reduced by 50%
 1. The fluid of hydrosalpinx may constitute a
mechanical barrier to implantation by causing the
embryo to float
2. Hydrosalpinx fluid is deficient to support the
developing embryo
3. Hydrosalpinx is toxic to the developing embryo}.
Aboubakr Elnashar

27.  TT:
1. Salpingectomy by laparoscopy: improvement of
outcomes (NICE, 2004)
2. Tubal occlusion at its uterine end by
laparoscopy (clipping the tube)
. These procedars are invasive and carry the risk of injury
to bowels, and blood vessels especially in the presence
of dense pelvic adhesions (scar tissues).
3. Tubal occlusion from its proximal ends through
hysteroscopy using Essure: an alternative in
these cases.
Aspiration of the fluid from the tube
Aboubakr Elnashar

28.  Male factor:
In IVF: poor success rates due to poor
fertilization rate
In ICSI: dramatic improvement in the
outcome.
Aboubakr Elnashar

29.  Endometriosis:
• Minimal & mild: No effect
(Vrtovec et al,2000)
• Moderate & severe:
 The fertilization rate, PR , & LBR were significantly
lower
(Azim et al,1999; Garrido et al, 2000; Harp et al BJOG 2014).
 On other hand, HFEA database (2000)
did not show lower PR in endometriosis, but it did not
take into account the stage of endometriosis.
Aboubakr Elnashar

30.  Fibroid:
Fibroids not causing deformity of the uterine cavity &
<5 cm did not affect the implantation or miscarriage
rate (Hart et al , 2001).
Aboubakr Elnashar

31. VII. Body weight
 BMI
 Ideal: 19-30
 outside this range: reduce the success of ART
(NICE,2004).
Obese women take longer to conceive and are at
higher risk of miscarriage
(Linsten et al 2005; Fedorcsak et al; 2004).
 BMI has no effect on PR but that the android body
fat distribution
 (Wass et al, 1997)
 WHR
 >0.8: PR is 16%
 0.7-0.79: PR is 30%.
{Excessive androgen levels have a negative effect on
oocyte development: poor quality embryo}
Aboubakr Elnashar

32. VIII. Lifestyle factors
 Smoking (maternal or paternal)
 significantly lower IVF.
(14% Vs 21%)
(Feichtinger et al,1997)
 reduce implantation and PR
(Neal et al, 2005).
 adversely affects LBR equivalent to increased
female age by 10 years
(Linsten et al, 2005).
Aboubakr Elnashar

33.  Alcohol
Consumption of more than one unit (12 g) per day
reduces the effectiveness of IVF
(NICE,2013)
 Caffeine
(over 2-50 mg/d Vs 0-2 mg/d; 100 mg 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).
Aboubakr Elnashar

34. Race
lower success rates following infertility treatments
in black, Hispanic and Ascian women compared to
white women regardless of the weight.
{fat distribution, also black and Ascian women are
more likely to have uterine fibroids}
(Luke et al,2011)
Emotional distress
Distress is unlikely to affect chances of pregnancy
after IVF treatment.
(Boivin et al, 2011)
Aboubakr Elnashar

35. Aboubakr Elnashar

36. I. COS
 COS: creation of numerous embryos, which could
be available for transfer or cryopreservation:
increasing the chance of pregnancy
(Wang et al,1994).
Natural cycle or CC stimulated IVF have poor
success rates/cycle compared to GnRha and Gnt
GnRha in addition to Gnt: higher PR and LBR than
using Gnt alone.
Aboubakr Elnashar

37. long protocol Vs Short & ultrashort
(Cochrane review, 2000)
superior in terms of
1. follicular development &
2. fertilization rate
3. number of embryos suitable for transfer
4. PR
5. more units of GN were needed
 Midluteal is the optimal Gnt suppression &
oocytes
(Roman et al 1992,Huirne et al,2004)
Aboubakr Elnashar

38. ,
 rFSH Vs other GN (HMG, hp-FSH, p-FSH), no
evidence of difference in LBR or OHSS
 42 trials, 9606 couples
 Further research on these comparisons is unlikely to
identify substantive differences in effectiveness or
safety
(Cochrane Database Syst Rev. 2011, Wely et al)
 Use either u or rec Gnt for ovarian stimulation
(NICE, 2013)
Aboubakr Elnashar

39.  Agonists Vs Antagonists
 LBR after COS for IVF does not depend on
the type of analogue used for pituitary
suppression
(SR: Kolibianakis et al,2006)
 Antagonist protocol:
 short, simple protocol with significant
decrease in severe OHSS & amount of GN.
 CPR, OPR/LBR were lower in antagonist
group
(Cochrane Database Systematic Review Al-Inany et al., 2006)
 No evidence of a difference in LBR
(Cochrane Database Syst Rev. 2011, Al-Inany et al, 2011)Aboubakr Elnashar

40. Gnt are comparably effective and safe.
The differences in isoform profile did not appear
to have clinically significant effects in IVF or ICSI
cycles.
some advantage of HP-hMG in terms on live
birth, and addition of rLH may be benefi cial in
certain groups of women. However, differences
were
small.
The choice depend upon
1. availability
2. convenience
3. costs. Aboubakr Elnashar

41. 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

42. III. Laboratory
1. ICSI Vs IVF:
 Borderline semen:
ICSI: higher fertilization rates
(van Rumsteke et al, Cochrane library, 2002)
 Normal semen:
ICSI: higher fertilization rates/oocyte injected but not
/oocyte retrieved compared to conventional IVF.
Aboubakr Elnashar

43. Tubal factor infertility:
IVF should be the initial tt of choice
(Aboulghar et al,1996; Bukulmez et al,2000).
{No significant difference in PR or take-home baby}.
Unexplained infertility:
ICSI should be 1st option
(Sertac et al,2000).
{Complete fertilization failure was higher in IVF
(34.3%) than ICSI (10.3%)}
(Jaroudi et al,2003).
Aboubakr Elnashar

44. 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).
Aboubakr Elnashar

45. 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 increases PR by 11%
(Wang et al, 1994)
Aboubakr Elnashar

46. 3. Assisted hatching
 Creations of an opening in z pellucida
either mechanically (partial zona dissection) or
chemically (zona drilling with acid Tyrode) or by
laser , before ET.
 Significant increases CPR in RIF
(Three RCTs: Chao et al., 1997; Magli et al., 1998; Nakayama et al.,
1999; Metaanalysis, Martins et al, 2011)
 Controversial
(Sallam, 2003).
in selected groups:
improvement of PR and LBR.
Aboubakr Elnashar

47. Although CPR was significantly higher, there was
no effect on the ‘take home-baby rate’
Systematic review of 23 RCTs (2572 women)(Edi-Osagie et al., 2003).
 No benefit of laser-AH in RIF
European multicentre randomized trial (Primi et al., 2004)
 Laser-assisted hatching:
RIF
Poor embryo quality
>38 years.
(ASRM, 2008)
Aboubakr Elnashar

48. 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.
Aboubakr Elnashar

49. (Buckett Fertil Steril. 2006; Abou-Setta et al
Reprod Biomed Online 2007; Brown et al
Cochrane Database Syst Rev 2010; Abou-
Setta et al. Cochrane Database 2009; Derks
et al Cochrane Database Syst Rev. 2009;
Bontekoe et al Cochrane Database 2014;
Cheong et al Cochrane Database Syst Rev.
2013; Craciunas et al Fertil Steril 2014;
Gaikwad et al Fertil Steril 2013)
Aboubakr Elnashar

50. 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):
blastocyst transfer result in improvement in PR and
LBR with lower incidence of multiple pregnancy
rates{transfer of less number of embryos}.
Aboubakr Elnashar

51. Age group
less than
35
35-37 38-40 41-42 43 or over
Blastocyst
transfer
44.3% 37.6% 29.4% 18% 7.5%
Cleaved
embryo
transfer
37.6% 32.7% 24.4% 14.3% 5.7%
LBR/cycle using donated own eggs.
SART report 2000
Aboubakr Elnashar

52. 3. Type of ET catheter:
PR was significantly higher in soft catheter
(van Weering,2002).
Aboubakr Elnashar

53. 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
Aboubakr Elnashar

54. 5. Site of embryo deposition
IR was significantly higher when the embryos were
deposited 2 cm below the uterine fundus
(Coroleu et al ,2002).
Aboubakr Elnashar

55. 6. Number of embryo transferred
• To balance the chance of a LB & the risk of MP, no
more than 2 embryos should be transferred
(NICE, 2004; HEFA, 2000)
• a maximum of 3 embryos may be replaced per for
women aged 40 or older but for women aged 39 years
and younger, the maximum is two embryos
(HFEA, code of practice, 2007).
• The aim is to reduce the risk of multiple pregnancy
Aboubakr Elnashar

56. Number of
embryos
replaced
Live birth rate
per cycle
Multiple
pregnancy rate
One 6.8% 4.7%
Two 16.8% 24.3%
Three 21.4% 32.6%
HFEA Report 1997
Aboubakr Elnashar

57. LBR for tt where 2 embryos are transferred
(provided that ≥4 embryos were created) is almost
identical to the LBR for tt where 3 embryos are
transferred but with a lower MPR
eSET for selected patients:
woman aged 35 or younger
first IVF tt
several good quality embryos.
{to reduce MPR}.
success rates comparable to double embryo
transfers if cumulative PR are calculated from both
fresh and subsequent frozen transfers.
Aboubakr Elnashar

58. Number of
embryos
replaced
LBR/cycle MPR
2 26.4% 26.0%
3 26.0% 34.3%
HFEA Report 1998
Aboubakr Elnashar

59. V. Luteal phase support
1.IM Vs oral:
IM P conferred the most benefit compared with oral P
(MA 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).
Aboubakr Elnashar

60. 3. Addition of E:
1. No advantage
(Lewin et al, 1994; 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).
Aboubakr Elnashar

61. 4. Addition of Prednisolone
Addition of Low dose aspirin
No benefit on PR , but it may reduce the rate of
spontaneous pregnancy loss
(Mollo et al,2003)
Addition of ascorbic acid
No benefit
(Griesinger et al, 2002)
Aboubakr Elnashar

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