Embryo transfer: Aboubakr Elnashar

1. EMBRYO TRANSFER
Prof. Aboubakr M Elnashar
Benha University Hospital
elnashar53@hotmail.com
Facebook:
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2. Contents
1. TIMING
2. ET CATHETERS
3. LOADING OF THE ET CATHETER
4. TECHNIQUE
5. FACTORS AFFECTING SUCCESS
6. DIFFICULT ET
CONCLUSION
6
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3. The final, yet crucial step in IVF.
Meticulous technique is essential for IVF success.
1. TIMING
ET is usually performed 2-5 d after OR
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4. 2. ET CATHETERS
Different types
varying in length, diameter, stiffness, memory
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5. ET Catheters
Labotect
WallaceCook
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6. 1. OUTER SHEATH
a thick hollow plastic tube (catheter ) with a bulb
(Guide catheter) , stopper; and markings.
Bulb helps the doctor to bypass the blind
endocervical crypts which line the cervical canal and
can cause the tip of the catheter to get trapped.
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7. 2. OBTURATOR
fits snugly within the outer sheath.
made of metal: allows the doctor manipulate the
outer sheath: can negotiate the curvature of the
endocervix.
3. INNER SHEATH
a soft tube, with markings at distal end of the tip.
The embryologist loads embryos into this sheath
and then hands this to the doctor.
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8. 3. TECHNIQUE
A. Before ET
1. Instruct patient to come fasting
{as a precaution in case the need for G A}.
2. Inform patient:
 fertilization rate
 number of available embryos
 number of embryos selected for the transfer.
 ET is a simple procedure.
 If she is much stressed: G A.
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9. 3. Revise:
 US picture of the uterus
 Dummy ET
1. length
2. direction of the uterus
3. cervico-uterine angulation
4. Lithotomy position:
-Cervix is visualized using Cusco’s speculum.
-Vaginal vaults are cleaned using tissue culture
media & sterile gauze.
-The cervical mucus at the external os is
aspirated gently & repeatedly using a 1 cm3
syringe.
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10. B. Transfer
I. Standard technique
1. The loaded ET catheter is introduced through
the cervix to pass the internal os under US
guidance.
& then gently advanced in the mid-uterine
cavity& stopped from 1–2 cm short of the fundus.
2. {Some patients experience suprapubic
heaviness& discomfort}.
After 1-2 min, when this complaint disappears,
the embryos are ejected slowly
3. Catheter is left in situ for 30-60 sec
4. Pressure is kept on the plunger of the syringe
while slowly withdrawing the catheter out
avoiding negative pressure. AboubakrElnashar

11. C. After ET
1. The catheter is checked for any retained
embryos. If found, retransfer is done
immediately.
2. Bed rest:
30 min
12 H: Not necessary
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12. II External sheath 1st – ET= afterload technique=
(Adrienne et al, 2005) 2 -step catheter insertion(Esteve , 2014)
1. Under US guidance: outer sheath of (the
labotect) ET catheter is passed, just beyond
the internal os.
2. The inner sheath is loaded by the embryologist
who then assist the physician in threading the
inner sheath into the external sheath.
•The inner catheter is slowly advanced by the
physician, and the embryos are deposited 1.0 cm
from the fundus (mid uterine cavity).
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13. 2- step catheter withdrawal (Esteve, 2014)
1. After 5–10 s: Soft catheter removed first
(pressure on the syringe plunger maintained)
while outer sheath withdrawn past internal os
Laboratory check
2. Rigid outer sheath removed and checked
One step catheter withdrawal (Adrienne et al, 2005)
The catheter is gently rotated and removed (with
keep the plunger of the catheter depressed until it
had been completely removed from the cervix)
over 15 s.
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14. Advantages
improve CPR by
1. Facilitating the ease of ET
2. Decrease the interval time of the procedure
3. Decrease the usual contamination of ET
catheter with mucous and/or blood.
 useful in centers
training physicians to perform ET with no
additional cost on the patient.
video
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15. 4. FACTORS AFFECTING SUCESS
A. Before ET
1. Embryo Selection
•ESET necessitates proper embryo selection
•Selection
1. Morphological criteria:
graduated embryo score
(Fisch et al).
2. Other criteria:
Early cleavage
Prolonging embryo culture to the blastocyst stage
PGD AboubakrElnashar

16. 2. The best day for ET:
•D2 Vs D3:
Although an increase in PR with D3 ET, there is no
sufficient good quality evidence to suggest an
improvement in live birth (Oatway et al, 2004, Chocrane library).
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17. •D 2 or 3 (early) Vs D5 or 6 (late):
Blastocyst transfer
Significantly higher CPR
(Guerif et al., 2004; Levitas et al., 2004).
{Improved embryo selection and uterine
receptivity}
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18. Advantages of blastocyst tansfer
1) minimizing exposure of embryo to hyper-
stimulated uterine environment
2) supplying better physiological synchronization
between embryo stage and the endometrium at
the time of ET
3) optimizing selection of embryos with increased
implantation potential
4) increasing the possibility to undergo
cryopreservation
5) reducing uterine contractions
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19. Drawbacks.
1. some cleavage embryos do not develop into
blastocysts in vitro
2. some blastocysts can not be well cryopreserved.
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20. 3. Cervical infection:
diminishes the P & IRs significantly.
PR for patients with positive cultures: 21%
patients with negative cultures: 38.4%
(Sallam et al , 2003; meta-analysis)
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21. 4. Use of antibiotics:
from the day of OR up to 6 days
(Amoxicillin + Clauvulanic acid)
does not improve IR
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22. 5. Choice of the Catheter
•The ideal ET catheter
soft
{avoid any trauma to endocervix or endometrium}
malleable
{find its way through the cervical canal into the
uterine cavity}.
•The outer rigid sheath should be minimally used to
stop short of the internal cervical os.
•If the outer sheath is introduced first, it will convert a
‘‘soft’’ catheter into a ‘‘stiff’’ catheter.
• ET catheter passing through the internal cervical os
can initiate contractions.
•Soft catheters: higher PR compared to firm
catheters. AboubakrElnashar

23. Soft catheters versus rigid catheters
Soft catheters Rigid catheters
• Cook
• Wallace
• TDT
• Frydman
• Tomcat
• Rocket
Buckett, Fertil Steril 85: 728, 2006
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24. 6. Mock (dummy, trial) ET (Sharif et al.1995)
AIM
1. Length of the uterine cavity& cervical canal
2. Direction of the uterine cavity& cervical canal
2. Cervico-uterine angulations.
3. Choose the most suitable catheter
4. Discover any difficulty:
•pinpoint external os,
•cervical polypi or fibroids
•anatomical distortion of the cervix from previous
surgery or congenital anomaly.
 ease of transfer
need for instrumentation
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25. Timing:
1. Before the start of the IVF cycle (1month)
2. At the time of start of ovarian stimulation
3. At the time of OR
4. Immediately before the real transfer.
 The timing does not affect FR, IR or PR.
 Performing a mock ET at the time of OR, 3 to 5 days
before ET, does not have a deleterious effect on the
endometrium
(Katariya et al, 2007)
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26. uterine length and position changes with ovarian
stimulation challenging the role of trial transfer
(Henne et al., 2009)
RVF uterus at mock ET will often change position
during the actual procedure.
USG mock ET during the real ET is a better method
of judging the direction of the uterine Axis.
(Shamonki et al).
Value:
1. Diminishes the incidence of difficult ET
(Mansour et al.)
2. Increases IR & PR
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27. 7. ET Medium
A fibrin sealant added to the ET medium:
non-significant improvement in PR
benefit in elderly patients only
Fibrin glue (EmbryoGlue)
prior to ET: significant improvement in IR & PR
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28. 8. Ultrasound Before ET
Aim
1. Length of uterine cavity& cervical canal
2. Cervico-uterine angle.
(a) no angle
(b) small angle (<30)
(c) moderate angle (30–60)
(d) large angle (>60)
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29. 3. Fibroids that may be encroaching on the uterine
cavity or distorting the cervical canal
4. Uterine anomalies.
5. Contents of the endometrial cavity
e.g. newly developed hydrometra in patients with
hydrosalpinges:
Aspiration of the uterine fluid did not help
{its rapid reaccumulation}
Cryopreservation of the embryos for future transfer
after removal of the hydrosalpinges
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30. 6. Endometrial thickness
<8 mm: implantation cannot take place
>14mm: hinder implantation. However, not confirmed
7. Endometrial pattern
Homogeneous: predict an adverse outcome
Triple-line: associated with conception.
8. Endometrial volume by 3D
<2.5 mL on the day of ET: poor likelihood of
implantation.
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31. 9. Full Bladder
: straightening’’ the uterus: increases PR.
However, not confirmed.
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32. 10. Vigorous flushing of the cervical canal
with culture medium
: increases PR.
However, not confirmed
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33. 11. Uterine Relaxing Substances
Progesterone:
starting on the day of OR. not improved PR
compared to starting on ET day.
NSAIDs: .
10 mg piroxicam (feldene), 1-2 h before ET:
significant improvement of I& PR
Sedation with 10 mg valium:
30 min-1 h before ET:
did not make any difference.
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34. Tocolytic agents or prostaglandin synthetase
inhibitor:
No a significant effect.
Sublingual GTN before ET:
smoother technique, shorter time of cervical
manipulation & higher PR.
Propofol G anesthesia for ET:
did not have a significant effect.
Can be used severe stress& anxiety
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35. 12. Experience of the Provider
•A significant difference in PR was found between the
10 clinicians
•Trained nurses Vs clinicians
No significant differences in IR & PR
•The minimal number of ETs necessary to acquire
proper experience:
50 ETs.
AboubakrElnashar

36. 13. Endometrial trauma by ET trials
performed either
during the preceding cycle (on D21 of the
previous cycle) or
on D6 of the COH cycle does not improve PR
(Yoldemir, Erenus, 2011)
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37. B. During ET
1. Position of the Patient
knee-chest position Vs dorsal position:
No significant difference in PR or EP (3.5 Vs 5.4%)
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38. 2. Analgesia &Anesthesia
•No significant difference in PR
•Acupuncture:
significantly higher PR than those who did not.
•Hypnosis:
significantly higher IR& PR
However not confirmed
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39. 3. US-Guided ET
•Catheters with echodense tips
Value:
1. Uterocervical angle immediately prior to ET:
bend the catheter accordingly: minimize trauma
to the cervical canal&/or the endometrium.
2. Visualize the tip of the ET catheter& the exact
site of embryo deposition
3. Confirm that the embryo-associated air bubble is
not displaced after ET.
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40. Baba et al.
80% of the embryos implant in the areas to which they
were initially transferred.
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41. Transvaginal ultrasound-directed ET
Anderson et al, Fertil Steril 77 (4): 769, 2002AboubakrElnashar

42. 4. Air in the ET Catheter
•Krampl et al; Moreno et al.
bracketing the embryo- containing medium by air
bubbles: tracking the air on the US to localize the
embryos after the ET
Not affect PR
•Eytan et al.
air blocked the transport of the transferred liquid
toward the fundus: ET catheter should contain
minimal volumes of air {enhance the embryo s
chances of reaching the site of implantation}
AboubakrElnashar

43. 5. Removing Cervical Mucus
By
1. Cotton swab & sterile saline initially, then
culture media.
2. Aspiration using
1 cm3 syringe with its tip placed at the external
os or
a soft catheter attached to a syringe.
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44. 6. Ensuring that catheter has passed
internal os & not kinked or curved:
How to know?:
Rotating the catheter by 360 C:
If it recoils: it is curved inside the cervical canal.
:Gently maneuver the vaginal speculum (the degree
of opening& how far it is pushed inside): facilitate
entering the catheter
How to avoid?
1. Dummy ET right before the actual one
2. Revise the previously performed US: curve the catheter
before loading
A situation in which you need to curve the catheter while you
have the embryos loaded should be completely avoided.
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45. 7. Gentle& Atraumatic Technique
•Even in introducing the speculum
{avoid unnecessary pushing of the cervix}.
•Difficulties during ET:
1. Difficulty in negotiating the cervical canal
2. Necessity of using a volsellum
3. Presence of blood after ET.
Only the presence of blood on or in the catheter
decreased PR& IR significantly.
(Alvero et al.)
{ET can cause rapid pressure fluctuations in the transferred
liquid}: transfer the embryo gently with minimum ejection
speed {avoid exposing the embryo to the steep pressure
gradient}.
(Grycrouk et al, 2011) AboubakrElnashar

46. Difficult Vs easy ET
Difficult ET diminish the PR (22.3 Vs 31%) & IR
significantly
(M A, Sallam et al, 2003).
{Trauma to the endocervix& endometrium}.
Murray et al.
used hysteroscopy: no clear association between
perceived difficulty of transfer& amount of
endometrial damage.
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47. 8. Avoid Touching the Uterine Fundus
•Place the catheter 1.5 cm from the fundus.
•Coroleu et al.
IR was significantly higher when the embryos were
deposited 2 cm below the uterine fundus compared
to when deposited 1 cm below the fundus.
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48. 9. Site of Embryo Deposition
=The relative position of the catheter tip within the
uterine cavity
•Depositing the embryos in the miduterine:
distance between the tip of the catheter and the
uterine fundus at transfer 1.5–2 cm:
Better IR
lower incidence of EP
•Measure the cervical canal& uterine cavity during
dummy ET or by US AboubakrElnashar

49. •Maximum implantation point (MIP) (Gergely et al) :
Point of intersection of the two imaginary lines formed by
extending the Fallopian tube course inside the uterine
cavity
Using 3D US
Embryos deposited at the MIP: good IR & PR
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50. 10. Time Interval between Embryo Loading
& Discharging
Matorras et al.
The longer: the lower PR & IR
An interval >120 sec: poor prognosis.
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51. 11. Withdrawal of the Catheter After ET
•Wait 60 sec after introducing the catheter into the
uterus before ejecting the embryos
•Wait another 60 sec before catheter withdrawal
{uterus can stabilize} .
•Immediate Vs slow withdrawal
Delay of 30 sec before withdrawing the catheter: improved
PR
{Negative pressure of capillary action created by withdrawing
the catheter could draw embryos into the cervical canal}
(Martinez et al.,2000)
No statistically significant difference in the PR
(Zeck et al., 2004)
Rotating the catheter 180 prior to removal
following ET (Neithardt et al, 2005)
Wait before injection, slowly inject, wait before withdrawal, slowly withdraw
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52. 12. Gentle mechanical pressure on the Cervix
•Mansour
using the vaginal speculum during & for 7 min after ET:
significantly improved IR&PR {decreased E expulsion}
(A) The two valves of the vaginal speculum are closed on the cervix.
(B) In the control group, the two valves of the vaginal speculum are open.
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53. 13. Retained Embryos
•Immediate retransfer did not have an adverse
effect on the pregnancy outcome.
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54. C. After ET
1. Bed Rest
•1 h Vs 24 h
No statistically significant difference in PR (21.5 Vs
18.2%)
IR was significantly higher (14.4 Vs 9%)
•Immediate ambulation Vs 1-2 h
No adverse effect on PR
{Endometrial cavity is a potential space.
ET catheter only separates the opposed endometrial
surfaces
Once the catheter is removed, the endometrial
surfaces re-oppose}.
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55. 2. Sexual Intercourse
during the peritransfer period Vs abstinence
PR was not significantly different
IR was significantly higher
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56. 3. Medication after ET
-low-dose aspirin (75 mg/d)
Birth rate was significantly increased
not confirmed in other studies
-Sildenafil, vainal E2
Endometrium thickness <8 mm: Not significantly
improved endometrial thickness or blood flow
-Antibiotics
Benefits have not been confirmed by any RCT
AboubakrElnashar

57. At the time of ET, there was no evidence of
benefit with the following interventions:
full bladder
removal of cervical mucus,
flushing the endocervical canal or the endometrial
cavity.
We did not identify any eligible studies for dummy
transfer, changing patient position, the use of a
tenaculum, or embryo after loading
(Cochrane 2009)
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58. RCT
 significantly higher PR are obtained when ET is
performed under US guidance
embryos are deposited in the middle part of the
uterine cavity
atraumatic technique
low-dose aspirin is routinely administered
following the procedure
(Sallam, 2005)
leaving the embryos inside it for more than 120
s diminish PR significantly.
AboubakrElnashar

59. Not affect the results
Blood in the catheter
Air in the catheter
immediate removal of the catheter
performing two transfers in the same cycle
prolonged bed rest
sexual intercourse after embryo transfer
use of sildenafil
AboubakrElnashar

60. (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)
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61. May be beneficial; Limited evidence to draw firm
conclusion
Antibiotics pre-ET
Intrauterine hCG
Pre-cycle hysteroscopy
Trial transfer
Endometrial scratching
(Mansour et al Steril 2011; Santibañez et al Reprod Biol Endocrinol. 2014;
Pundir et al Reprod Biomed Online 2014)
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62. Cochrane reviews have concluded that the
live birth rate is not increased by
delaying embryo transfer from day two to three or
to the blastocyst stage
single ET leads to lower live birth rates than the
transfer of two embryos.
The value of a mock transfer a few days before
the actual procedure has been challenged as the
position of the uterus may change.
still to be determined.
The effect of holding the cervix with a volsellum,
routinely administering antibiotics
superiority of one catheter over the others
AboubakrElnashar

63. 6. DIFFICULT ET
Causes:
1. Tight or closed cervix
2. Anatomical distortion {fibromyomata or previous
surgical interference}.
The uterus is sometimes a little "tricky". Here it is distorted by myomas (fibroids), making the embryo transfer itself - and visualization with ultrasound difficult.
Same image: Uterus outlined in red, myoma in blue, endometrial lining outlined in green. Catheter needs to place embryos between green lines - in the orange area.
The uterus is sometimes a little "tricky". Here it is distorted by myomas (fibroids), making the
embryo transfer itself - and visualization with ultrasound difficult.
Same image: Uterus outlined in red, myoma in blue, endometrial lining outlined in green.
Catheter needs to place embryos between green lines - in the orange area.
AboubakrElnashar

64. ET is considered difficult when
1. additional instrumentation was required or
2. firmer catheter was used
3. required changing of catheter.
AboubakrElnashar

65. Treatment:
1. G anesthesia
(propofol 2 mg/kg as an induction dose & anesthesia is
maintained by inhalation of isoflurosane 1.5% & oxygen
100% through a facemask).
2. The dummy ET is repeated& if not successful:
tenaculum is used to stabilize the cervix.
3. Special rigid but malleable introducer
Curving a rigid but malleable embryo
transfer catheter according to the cervico-
uterine angle overcomes almost all
difficult cases
AboubakrElnashar

66. 4. US G transabdominal ET:
5. US G transvaginal transmyometrial ET
6. Cervical dilatation.
When:
in a cycle preceding the treatment cycle.
on the day of OR: results are unsatisfactory.
7. Hysteroscopic correction of cervical stenosis.
8. Hygroscopic rods for slow cervical dilatation e.g.
laminaria tents, hygroscopic cervical rods
9. Freezing the embryos& retransferring in a
subsequent cycle. AboubakrElnashar

67. AboubakrElnashar

68. CONCLUSIONS
•ET should be performed under US guidance and soft
catheters perform better than firm ones.
•The best site for embryo deposition is the midcavity
of the uterus,1.5- 2 cm below the fundus.
•Difficult transfers and cervical infection affect the
results negatively.
•There is no need for bed rest after ET and sexual
intercourse is permitted.
AboubakrElnashar

69. Thank you:
Aboubakr Elnashar
Facebook:
https://www.facebook.com/groups/227744884091351/
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70. 1. Suction mucous if present
2. Adjust shoulder at 5
3. Introduce under US
4. Be sure you are inside
5. Push 1 cm the soft one
6. Withdraw the introducer slowly
7. Inject while maintaining and maintain for 1.5
min
8. Rotate needle while withdrawing
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