1. Embryo transfer: factors involved in optimizing the success
Doç. Dr. Erdal Aktan
Özel Ege Tüp Bebek Merkezi,
IVF Center- Izmir
Çeşme

2. 2nd v 3rd day ET 3rd day ET increased PR
(OR 1.26 %95 CI ) 10 RCT
Groups are similar regarding OPR and LBR
(OR 1.05 %95 CI ve OR 1.07 %95 CI )
3 RCT
Cochrane Database Syst Rev 2004; 2:CD004378

3. Blastocyst v Cleavage ET
LBR per couple (OR 1.16, 95% CI )
2/3 day 34.3% vs 5/6 day 35.4% 7 RCT
PR per couple (OR 1.05, 95% CI )
2/3 day 38.8% vs 5/6 day 40.3% 15 RCT
Groups are similar regarding multiple pregnancy rate (OR 0.85, 95% CI )
12 RCT
Cochrane Database Syst Rev 2005 Oct 19;(4):CD002118

4. Blastocyst v Cleavage ET
n of Couples with spare embryos to freeze
more in cleavage ET group
ET cancellation: more in blastocyst ET group
Subgroups with good prognostic criteria are similar regarding ET cancellation rate
Cochrane Database Syst Rev 2005 Oct 19;(4):CD002118

5. n of embryos transferred: 2 v 3 embryos
Retrospective cohort study
1448 women & 4004 embryos transferred
Only 1st IVF cycles
At least 6 embryos eligible for ET in every cycle
Salha O et al, J Assist Reprod Genet Jul;17(6):335-43

6. n of embryos transferred: 2 v 3 embryos
Women <35 y with good quality spare embryos:
PR are similar
LBR (total) are similar
Twins and triplets are more frequent in 3 ET group
Salha O et al, J Assist Reprod Genet Jul;17(6):335-43

7. n of embryos transferred: 2 v 3 embryos
Women <35 y without good quality spare embryos:
In 3 ET group
PR (39.3 vs 28.8%; P = 0.04)
Total LBR (32.7 vs 19.4%; P = 0.02)
LBR (single)
Multiple PR are similar
Salha O et al, J Assist Reprod Genet Jul;17(6):335-43

8. n of embryos transferred: 2 v 3 embryos
Women >35 y with or without good quality spare embryos:
Clinical results are better in 3 ET group
Multiple PR are similar
Salha O et al, J Assist Reprod Genet Jul;17(6):335-43

9. n of embryos transferred: 2 v 3 embryos
Conclusion: Optimal n of embryos for transfer depends on
Quality of embryos
Age of women
Presence of good quality spare embryos
Salha O et al, J Assist Reprod Genet Jul;17(6):335-43

10. n of embryos transferred: 2 v 3 embryos
Retrospective analysis
ET policies during two different periods
Morphologic scoring, best embryos for ET
<36 y, 2ET v 3ET:
PR % v 55.7% (p<0.01)
Twin rates are similar
Triplets 0 v 6.8%
Setti PE et al, Reprod Biomed Online Jul;11(1):64-70

11. eSET v DET 3 RCT Meta-analysis: (OR 9.97 %95 CI 2.61-38.19)
PR per woman DET
(OR 2.08 %95 CI )
LBR per woman DET
(OR 1.90 %95 CI )
Multiple PR DET
(OR 9.97 %95 CI )
Cochrane Database Syst Rev 2004; 4:CD003416

12. eSET v DET 4 RCT meta-analysis (fresh cycles) eSET: LBR , MPR
eSET + 1 FET (subsequent cycle): groups are similar regarding cumulative LBR and CPR
Pandian Z et al. Hum Reprod 2005; 20:
Single blast v single cleavage ET (<36 y)
%32 v 26.1 RR 1.48 %95CI RCT
Papanikolau EG et al. N Engl J Med Mar 16;354(11):

13. Economic evaluations of eSET v DET
It can be concluded that DET is the most expensive strategy.
DET is also most effective if performed in one fresh cycle.
eSET is only preferred from a cost-effectiveness point of view when performed in good prognosis patients and when frozen/thawed cycles are included.
If frozen/thawed cycles are excluded, the choice between eSET and DET depends on how much society is willing to pay for one extra successful pregnancy.
Fiddelers AA et al. Hum Reprod Update Jan-Feb;13(1):5-13.

14. ET Catheters

15. ET Catheters Tight Difficult Transfer (TDT) Catheter (Hard catheter), The Worst One

16. ET Catheters Soft Catheters: Cook v Wallace

17. ET Catheters
Abou-Setta A et al. Hum Reprod 2005; 20:

18. Mock embryo transfer During the luteal phase of previous cycle
On the day of oocyte retrieval
Just before the real transfer
To choose the right catheter and determine the axis of the uterus

19. Mock embryo transfer
Reduces the risk of difficult transfer, increases IR and PR
Mansour R et al, Fertil Steril 1990; 54:
Uterus at mock embryo transfer will often change position at real embryo transfer
(RV AV)
Henne MB, Milki AA, Human Reprod 2004; 19:
Moulding the catheter according to the uterocervical angle measured by ultrasound increases CPR & IR
Sallam HN et al, Human Reprod 2002; 17:

20. Endometrial assessment
Endometrial thickness in pregnant and nonpregnant groups are similar
Rashidi BH et al. Eur J Obstet Gynecol Reprod Biol ;120(2):179-84
Schild RL et al. Hum Reprod 1999; 14:
Laasch C, Puscheck E. Assist Reprod Genet 2004; 21:47-50

21. Endometrial assessment
In oocyte recipients who shared oocytes from the same donor and showed discordant pregnancy outcome:
Endometrial thickness in pregnant and non-pregnant groups are similar
(Matched pair analysis)
Garcia-Velasco JA et al. Fertil Steril 2003;80:54-60

22. Endometrial assessment
Endometrial thickness predicts PR in IVF cycles
McWilliams GD et al. Fertil Steril 2007;88:74-81
Kovacs P et al. Hum Reprod. 2003;18:
In “<8 mm endometrial thickness group” PR is significantly decreased
Noyes N et al. Fertil Steril 2001; 76:92-97
Zenke U et al. Fertil Steril 2004; 82:
Ardaens Y et al. Gynecol Obstet Fertil 2002; 30:

23. Endometrial assessment
The chances of achieving a thick endometrium for patients >40 years of age are lower than for younger patients.
A thicker endometrium is correlated with a higher PR only for patients >35 years of age
Amir W et al. Fertil Steril 2007;87:
Endometrial thickness is independently and significantly related to higher pregnancy rates in IVF cycles of women 40 y and older
Tsafrir A et al. Reprod Biomed Online 2007 Mar;14(3):348-55

24. Endometrial assessment
Endometrial pattern is similar in pregnant and non-pregnant groups
Noyes N et al. Fertil Steril 2001; 76:92-97
Rashidi BH et al. Eur J Obstet Gynecol Reprod Biol ;120(2):179-84
Triple-line pattern group had significantly higher PR campared with homogenous pattern
Jarvela IY et al. Ultrasound Obstet Gynecol. 2005;26:
The effect of pattern on the day of OPU is more important than the one on hCG day
Sharara FI et al. J Assist Reprod Genet. 1999;16:

25. Effect of “provider at ET”
10 different providers had significantly different PRs during 854 fresh ETs.
Hearns-Stokes RM et al. Fertil Steril 2000; 74:80-86
Appropriately trained nurses and doctors had similar IR/PR
Barber D et al,Hum Reprod. 1996; 11:
Sinclair L et al, Hum Reprod. 1998; 13:
Bjuresten K et al, Acta Obstet Gynecol Scand 2003; 82: (RCT)

26. Effect of “provider at ET”
Experienced (training completed) and inexperienced (training ongoing) nurses are compared:
Nurses in a given group are similar regarding results
Groups are significantly different regarding results (29.5% v 19.5%, p<0.02)
Barber D et al, Hum Fertil (Camb) 2000; 3:

27. Effect of “provider at ET”
Learning curve:
ET trainees can reach an acceptable PR after the first ETs.
Clinical pregnancy rates of fellows-in-training were indistinguishable statistically from those of experienced staff by 50 transfers.
(45.5% v 47.3%)
Papageorgiou TC et al. Hum Reprod 2001; 16:

28. Effect of difficult ET
Sallam HN. Curr Opin Obstet Gynecol 2005; 17:

29. Effect of difficult ET
ETs in 584 IVF cycles, only GI, II or blastocysts transferred, 10 physicians
Parameters
Blood on catheter (10.3%)
Mucus on catheter (20.7%)
Retention of embryos in catheter (5%)
Aborted first attempt at ET (8.9%)
Difficult ET as judged by provider (10%)
Need for mock embryo transfer immediately before the actual transfer (6.7%)
Alvero R et al, Hum Reprod. 2003;18:

30. Effect of difficult ET
Presence of blood on or in the catheter negatively affected the IR and PR.
(31.3% v 19.5% p=0.015) and (51.7% v 31.7% p=0.004)
None of the other factors significantly affected PR.
Alvero R et al, Hum Reprod. 2003;18:

31. Tenaculum placement
Tenaculum placement during ET increases oxytocin concentration and “junctional zone” contractions
Dorn C et al, Eur J Obstet Gynecol Reprod Biol 1999; 87:77-80
Lesny P et al, Hum Reprod 1999; 14:
Frequency of uterine contractions is negatively correlated to IR & PR
(embryos are expelled ?)
Fanchin R et al. Contracept Fertil Sex. 1998; 26:

32. Tenaculum placement
Tenaculum (volsellum) placement during ET did not have any significant effect on PR & IR
Tenaculum placement ET v easy transfer
(PR & IR)
OR=0.71 (95% CI ) & OR=0.97 (95% CI )
Sallam HN et al. J Assist Reprod Genet Apr;20(4):

33. Ultrasound-guided embryo transfer: immediate withdrawal of the catheter versus a 30 second wait
Does failing to withdraw catheter immidiately after ET causes uterine contractions which can lower PR?
PR: %60.8 v 69.4% p>0.05 RCT
Martinez F et al. Hum Reprod May;16(5):871-4

34. Time interval between embryo catheter loading and discharging
The longer the duration, the lower the PR and IR.
The decrease in PR and IR is gradual until a duration of 120 s, and decreases sharply afterwards.
Matorras R et al, Hum Reprod. 2004; 19:

35. Impact of retained embryos on the outcome
% of all transfers
Retained embryos in the transfer catheter and immediate retransfer of them have no adverse impact on clinical pregnancy*, implantation**, and live birth rates***
Vicdan K et al. Eur J Obstet Gynecol Reprod Biol. 2007;134:79-82 */**
Lee HC et al. Fertil Steril 2004;82:334-7*/**/***
Alvero R et al. Hum Reprod. 2003;18: **
Tur-Kaspa I et al. Hum Reprod. 1998;13:2452-5*
Nabi A et al. Hum Reprod. 1997;12: *

36. Impact of retained embryos on the outcome
Retained embryos in the transfer catheter and immediate retransfer of them have adverse effect on CPR.
Visser DS et al, J Assist Reprod Genet Jan;10(1):37-43

37. US Guided ET Observation of ET catether tip
Observation of the embryo discharge site
Observation of the air bubble
Prevents touch to fundus (contractions ?)
Discharge 1-2 cm to fundus

38. US guided v clinical touch
5968 ET in 20 RCT
Meta-analysis
Abou-Setta AM et al. Fertil Steril. 2007;88:333-41

39. US guided v clinical touch
Abou-Setta AM et al. Fertil Steril. 2007;88:333-41

40. US guided v clinical touch

41. US guided v clinical touch

42. US guided v clinical touch

43. US guided v clinical touch
In US guided ET group:
IR OR = 1.35, 95% CI =
Difficult ETR OR = 0.68, 95% CI =
Similar for MPR, ectopic & miscarriage rates
Abou-Setta AM et al. Fertil Steril. 2007;88:333-41

44. Influence of embryo transfer depth
For every additional millimeter embryos are deposited away from the fundus, the odds of clinical pregnancy increased by 11%
(OR=1.11 by multivariable logistic regression model)
Pope et al, Fertil Steril 2004; 81:51-58
Better IR & PR are obtained when the catheter tip is positioned close to the middle area of the endometrial cavity
Oliveira JB et al, Reprod Biomed Online 2004; 9:

45. Influence of embryo transfer depth
PR in 1 cm depth group was significantly lower than in 1.5 cm and 2 cm depth groups
Coroleu B et al. Hum Reprod. 2002;17:341-6
The IR & PR were similar whether the embryos were deposited in the upper or lower half of the endometrial cavity
Franco JG Jr et al. Hum Reprod ;19:

46. Influence of embryo transfer depth
PR, OPR, and IR are higher when the air bubble is at the upper half of the endometrial length
Schats R et al. Hum Reprod 2006; 21(Supp 1):i82
ESHRE 2006 Abstracts Book (O-210)

47. Bed rest versus free mobilisation following ET
Immediate ambulation following the ET procedure has no adverse influence on the ability to conceive.
Bar-Hava I et al. Fertil Steril Mar;83(3):594-7
Sharif K et al. Fertil Steril 1998; 69:
One-hour*/20’** and 24-hour rest post-embryo transfer result in comparable rates of clinical pregnancy.
Amarin ZO, Obeidat BR. BJOG 2004; 111: * RCT
Botta G, Grudzinskas G. Hum Reprod 1997; 12: ** RCT

48. The effect of peri-transfer intercourse on pregnancy rates
Multicenter RCT
There was no significant difference between the intercourse and abstain groups in relation to PR
Hence exposure to semen around the time of embryo transfer increases IR
OR 1.48, %95 CI
Tremellen KP et al. Hum Reprod 2000; 15:

49. PIROXICAM RCT 10 mg Piroxicam v placebo 1-2 h before ET
IR (18.7% v 8.6% ) and PR (46.8% v 27.6% )
<40 y, fresh and frozen ET
Moon HS et al, Fertil Steril Oct;82(4):816-20

50. Antibiotic prophylaxis & IVF/ET
Amoxicilline + clavulanic acid prophylaxis
Only RCT on AB prophylaxis & IVF/ET
IR (36.9% v 36.5%; p>0.95)
Peikrishvili R et al. J Gynecol Obstet Biol Reprod (Paris). 2004;33:
Failure to conceive in ART is significantly associated with bacterial colonization of the uterine cervix
Salim R et al. Hum Reprod 2002; 17:
Positive microbiology cultures of embryo catheter tip is accociated with PR and IR
Prophylactic antibiotics are associated with a reduction in positive microbiology cultures of embryo catheter tips
Egbase PE et al. Lancet 1999; 354:

51. Aspirin & IVF/ET
Currently available evidence does not support the use of aspirin in IVF or ICSI treatment.* (PR & LBR)
However, the noted trend of improvement in clinical pregnancy, and the lack of power even when the studies were pooled highlight the need for a definitive trial.**
Khairy M et al. Fertil Steril Oct;88(4): Review/ Meta-analysis*/**
Gelbaya TA et al. Hum Reprod Update Jul-Aug;13(4): Review/ Meta-analysis*

52. Prednisolone Does not have any significant effect on IR & CPR
Lee KA et al. Hum Reprod 1994; 9:
Moffitt D et al. Fertil Steril 1995; 63: (RCT)
Motta GL et al. J Reprod Med 1996; 41: (RCT)
Fridstrom M et al. Hum Reprod 1999; 14: (RCT)
Ubaldi F et al. Hum Reprod 2002; 17: (RCT)

53. Adjuvant therapy with Sildenafil in IVF for endometrial development
While the use of adjuvant therapy did not significantly improve ultrasonographic endometrial thickness, it did improve outcome rates (PR&LBR).
Fratterelli JL et al. Reprod Biomed Online Jun;12(6):722-9.
Vaginal administration of sildenafil enhanced endometrial development in 70% of patients with previous poor (<9mm) endometrial development High IR & OPR were achieved in group with enhanced development. Previous endometritis may decrease the response to sildenafil.
Sher G and Fisch JD. Fertil Steril Nov;78(5):

54. Thanks for your attention