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Optimizing Embryo Transfer in
IVF Cycles
Ulun ULUG, M.D.
Istanbul
Optimizing IVF Outcome
Precongress Course
TAJEV 2014
Embryo transfer is the rate limiting step in
the process of ART
Successful ART
1. Uterine receptivity
2. Embryo quality
3. Embryo transfer
Is Embryo Transfer Procedure Inefficient?
 Dummy ET using methylene blue
(Mansour et al 1994
The dye was extruded at the external cervical
os in 23% to 57% cases
 First IVF pregnancy was ectopic
(Edwards and Steptoe, 1975)
What may go wrong during transfer ?
1. Distruption of endometrium
2. Induction of uterine contractions
3. Deposition of embryos in a suboptimal location
4. Damage of embryos during the process
What is difficult Transfer ?
 Prolonged time to negotiate uterocervical angle
 Tenaculum application
 Blood in or on the catheter
 Stiff embryo transfer catheter
Why is it difficult to transfer ?
 Cervical stenosis
 Acute angle of uterocervical portion
(anteversion/retroversion)
 Unexperienced operator
Difficult Embryo transfer: analysis of 6484 transfers
Listijono et al, 2013
N (%) CPR/ET (%)
Easy 5976 (92.2) 30.7
Medium/Difficult 408 (7.8) 24.6
Effect of difficult ET
Sallam et al 2005
Umut IVF Center
01/2013-12/2013
Non-difficult
(n=1316)
Difficult
(n=28)
CPR 46.8 % 32.1%
Required sedation or tenaculum application with malleable Wallace catheter.
Blood was seen in catheters
Yaralı et al
Tenaculum placement
 Tenaculum placement during ET increases oxytocin
concentration and “junctional zone” contractions
Dorn C et al, 1999
Lesny P et al,1999
 Frequency of uterine contractions is negatively
correlated to IR & PR
Fanchin R et al. 1998
Where does the blood on the tip of
catheter come from?
Mock embryo transfer
 Reduces the risk of difficult transfer, increases IR and PR
Mansour et al,1990
 Uterus at mock embryo transfer will often change position
at real embryo transfer (Retroversion to anteversion)
Henne and Milki 2004
Steps during ET
1. Room conditions
2. Ultrasonography
3. Operator
4. Assistant and Embriologist
5. Preparation of cervix
6. Loading of catheter
7. Passing uterocervical angle
8. Deposition of embryos
9. Withdrawal of catheter
10. Patient instructions after ET
TIME
Room Conditions
1. Adjacent to IVF Lab
2. Operating room
3. Silent
4. Climate
5. Psychologic support
Seeing is Believing
ET and Ultrasonographic guidance
 Lesny et al, 1998
 30 µl Echovist injection
 45 min serial transvaginal sonograms
Location No Touch Twice Touch
No change 7 1
Changed - 6
Advantages of ultrasonographic guidance:
Less difficult transfers
Detection of catheter load inside uterine
cavity
Better position
Full bladder facilitates correction of acute
uterocervical angle
Sonography assistant is of importance:
1. Anatomical variations of genital tract complicates to
visualize sagittal section of cervical canal and
endometrial lining.
2. Furthermore stimulated ovaries hamper proper image
Experience of operator
Learning curve:
 ET trainees can reach an acceptable PR after the first
25-30 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 et al 20
Who will perform embryo transfer?
Loading Embryo to Catheter
 Embryos could expel into vagina, if transfer medium
exeeds 60 µl.
 Implantation could be affected when medium was less
than 10 µl .
Ebner T et al , 2001
Loading transfer catheter with only medium
or air/medium ?
Soft vs Stiff embryo transfer catheters
Preparation of cervix:
Removal of mucus
Abou-Setta et al
 Obstruct catheter tip
 Contamination with cervical flora
 Embryos can be embedded in mucus and dislodged
Cervical Mucus
Moulding the catheter (Sallam et al)
USG No USG
Difficult transfer 8.4% 26,8% 0,0001
Blood on tip 5% 13,4% 0,01
CPR 26,2% 18,4% 0,02
Ultrasound guidance and moulding the catheter facilitates
the transfer uterocervical angle
CPR
No angle 35,9%
<30 34,4%
30-60 31,1%
>60 16,9%
Single attempt Second attempt Third attempt
n 1135 61 8
CPR (%) 24,7 23,2 25
Nahi et al, 1997
Does standing upright immediately after ET affect
embryo position ?
(Woolcott et al, 1997)
 No movement occured in 94.1%
 <1cm movement in 4%
 1-5 cm in 2%
Post-embryo transfer interventions for women
undergoing in vitro fertilization (IVF) and intracytoplasmic
sperm injection
Abou-Setta et al Cochrane review
There was no evidence of an effect bed rest in improving the rate
of clinical pregnancies and miscarriages
Implantation site of embryo after transfer
Baba et al
Prospective controlled study
 22 pregnancies after ET
 80% of the gestational sacs were detected on the site of
air bubbles spreaded
Conclusion:
Factors affecting success after ET: proven
evidence based
 Ultrasound guidance
 Soft catheters
Conclusion:
Factors affecting success after ET: limited
proven evidence based
 Mid uterine position of catheter tip
 Shortening of loading and discharging interval time of
embryos
Conclusion:
Factors affecting success after ET: no proof
of benefit
 Use of mock transfer
 Use of cervical tenaculum
 Removal or flushing of the cervical mucus
 Antibiotic administration during ET
 Bed rest following ET
Dr. Ulun Uluğ
Dr. Selen Sezginsoy
Dr. Emre Bakırcıoğlu
Dr. Çiğdem Çizmeci
Lab:
Oya Yetiş
Habib Aslan
Munevver Serdaroğulları
Sinan Yıldız
Nurse Staff:
Hatice Özkan
Yasemin Köroğlu
Didem Yıldız
Ebru Köse
Hatice Duymaz
Gülseven Alıcı
Cennet Işık
Optimizing Embryo Transfer in IVF Cycles

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Optimizing Embryo Transfer in IVF Cycles

  • 1. Optimizing Embryo Transfer in IVF Cycles Ulun ULUG, M.D. Istanbul Optimizing IVF Outcome Precongress Course TAJEV 2014
  • 2. Embryo transfer is the rate limiting step in the process of ART
  • 3. Successful ART 1. Uterine receptivity 2. Embryo quality 3. Embryo transfer
  • 4. Is Embryo Transfer Procedure Inefficient?  Dummy ET using methylene blue (Mansour et al 1994 The dye was extruded at the external cervical os in 23% to 57% cases  First IVF pregnancy was ectopic (Edwards and Steptoe, 1975)
  • 5. What may go wrong during transfer ? 1. Distruption of endometrium 2. Induction of uterine contractions 3. Deposition of embryos in a suboptimal location 4. Damage of embryos during the process
  • 6. What is difficult Transfer ?  Prolonged time to negotiate uterocervical angle  Tenaculum application  Blood in or on the catheter  Stiff embryo transfer catheter
  • 7. Why is it difficult to transfer ?  Cervical stenosis  Acute angle of uterocervical portion (anteversion/retroversion)  Unexperienced operator
  • 8. Difficult Embryo transfer: analysis of 6484 transfers Listijono et al, 2013 N (%) CPR/ET (%) Easy 5976 (92.2) 30.7 Medium/Difficult 408 (7.8) 24.6
  • 9. Effect of difficult ET Sallam et al 2005
  • 10. Umut IVF Center 01/2013-12/2013 Non-difficult (n=1316) Difficult (n=28) CPR 46.8 % 32.1% Required sedation or tenaculum application with malleable Wallace catheter. Blood was seen in catheters
  • 12. Tenaculum placement  Tenaculum placement during ET increases oxytocin concentration and “junctional zone” contractions Dorn C et al, 1999 Lesny P et al,1999  Frequency of uterine contractions is negatively correlated to IR & PR Fanchin R et al. 1998
  • 13.
  • 14. Where does the blood on the tip of catheter come from?
  • 15.
  • 16. Mock embryo transfer  Reduces the risk of difficult transfer, increases IR and PR Mansour et al,1990  Uterus at mock embryo transfer will often change position at real embryo transfer (Retroversion to anteversion) Henne and Milki 2004
  • 17. Steps during ET 1. Room conditions 2. Ultrasonography 3. Operator 4. Assistant and Embriologist 5. Preparation of cervix 6. Loading of catheter 7. Passing uterocervical angle 8. Deposition of embryos 9. Withdrawal of catheter 10. Patient instructions after ET TIME
  • 18. Room Conditions 1. Adjacent to IVF Lab 2. Operating room 3. Silent 4. Climate 5. Psychologic support
  • 21.  Lesny et al, 1998  30 µl Echovist injection  45 min serial transvaginal sonograms Location No Touch Twice Touch No change 7 1 Changed - 6
  • 22. Advantages of ultrasonographic guidance: Less difficult transfers Detection of catheter load inside uterine cavity Better position Full bladder facilitates correction of acute uterocervical angle
  • 23. Sonography assistant is of importance: 1. Anatomical variations of genital tract complicates to visualize sagittal section of cervical canal and endometrial lining. 2. Furthermore stimulated ovaries hamper proper image
  • 24.
  • 25.
  • 26. Experience of operator Learning curve:  ET trainees can reach an acceptable PR after the first 25-30 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 et al 20
  • 27. Who will perform embryo transfer?
  • 28. Loading Embryo to Catheter  Embryos could expel into vagina, if transfer medium exeeds 60 µl.  Implantation could be affected when medium was less than 10 µl . Ebner T et al , 2001
  • 29. Loading transfer catheter with only medium or air/medium ?
  • 30. Soft vs Stiff embryo transfer catheters
  • 31.
  • 32.
  • 33.
  • 34.
  • 35. Preparation of cervix: Removal of mucus Abou-Setta et al  Obstruct catheter tip  Contamination with cervical flora  Embryos can be embedded in mucus and dislodged
  • 37.
  • 38. Moulding the catheter (Sallam et al) USG No USG Difficult transfer 8.4% 26,8% 0,0001 Blood on tip 5% 13,4% 0,01 CPR 26,2% 18,4% 0,02 Ultrasound guidance and moulding the catheter facilitates the transfer uterocervical angle CPR No angle 35,9% <30 34,4% 30-60 31,1% >60 16,9%
  • 39.
  • 40.
  • 41. Single attempt Second attempt Third attempt n 1135 61 8 CPR (%) 24,7 23,2 25 Nahi et al, 1997
  • 42.
  • 43.
  • 44.
  • 45.
  • 46.
  • 47. Does standing upright immediately after ET affect embryo position ? (Woolcott et al, 1997)  No movement occured in 94.1%  <1cm movement in 4%  1-5 cm in 2% Post-embryo transfer interventions for women undergoing in vitro fertilization (IVF) and intracytoplasmic sperm injection Abou-Setta et al Cochrane review There was no evidence of an effect bed rest in improving the rate of clinical pregnancies and miscarriages
  • 48. Implantation site of embryo after transfer Baba et al Prospective controlled study  22 pregnancies after ET  80% of the gestational sacs were detected on the site of air bubbles spreaded
  • 49. Conclusion: Factors affecting success after ET: proven evidence based  Ultrasound guidance  Soft catheters
  • 50. Conclusion: Factors affecting success after ET: limited proven evidence based  Mid uterine position of catheter tip  Shortening of loading and discharging interval time of embryos
  • 51. Conclusion: Factors affecting success after ET: no proof of benefit  Use of mock transfer  Use of cervical tenaculum  Removal or flushing of the cervical mucus  Antibiotic administration during ET  Bed rest following ET
  • 52. Dr. Ulun Uluğ Dr. Selen Sezginsoy Dr. Emre Bakırcıoğlu Dr. Çiğdem Çizmeci Lab: Oya Yetiş Habib Aslan Munevver Serdaroğulları Sinan Yıldız Nurse Staff: Hatice Özkan Yasemin Köroğlu Didem Yıldız Ebru Köse Hatice Duymaz Gülseven Alıcı Cennet Işık