factors affecting success of embryo transfer
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Factors affecting success of embryo transferReview of RCT and MA: From 1990-2004
Prof. Aboubakr ElnasharBenha university Hospital, Egypt
Embryo transfer (ET)
The least successful step in ART.
Many factors have been proposed to increase
the success of this step.
Various refinements of the technique of ET
have been suggested in order to improve the
pregnancy & implantation rates (P& IR).
However, many of these suggestions were
based on retrospective or observational studies.
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Our objective
To review RCT & meta-analyses concerning the factors
affecting the success of ET.
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Materials & methods
An electronic search of
the Chocrane library &
Pub Med for
RCT & meta-anylysis concerning ET
from 1990 to 2004.
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The Cochrane Collaboration Library
an outstanding effort to provide best evidence.
It is the best single source of evidence about the
effects of health care.
It is named after the British epidemiologist Archie
Cochrane
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The library is updated every 3 months.
It contains 4 sets of databases
1.Systematic reviews
2. Reviews of effectiveness
3.Controlled trial registry
4.Review methodology
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RCT
gold standard in clinical research.
the standard method for answering questions about
the effectiveness of different therapies
provides the strongest evidence for the cause &
effect relationship & is subject to the least amount
of bias.
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Systematic review
Review in which all the evidence pertaining to a
particular field of research has been collected
(via a systematic search of the literature &
unpublished sources) &
evaluated using predefined quality criteria.
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Meta-analysis
Systematic reviews in which the numerical results
of different studies have been combined using
standard statistical techniques.
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Results
2 Chocrane systematic reviews.
5 meta-analysis &
34 RCT.
Studies were reviewed as regard the factors
affecting success of ET. Factors were classified
into pre-transfer, transfer & post-transfer.
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1. Trial (dummy, mock) transfer:
Clinical P & IR are significantly increased in those patients who
had a trial transfer compared to those who did not
(Mansour et al, 1990).
Trial ET:
determines the most suitable catheter &
avoids unexpected difficult & failed ET.
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2. Embryo transfer by midwife or gynecologist:
Similar clinical PRs between Ets performed by midwives &
gynecologists (31% vs. 29%)
(Bjuresten et al,2003).
High acceptance of ET by a midwife. Importance of training
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3. The best day for embryo transfer:
Day 2 Vs day 3:
Although an increase in clinical 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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Day 2 or 3 (early)Vs day 5 or 6 (late);
Day 5 ET has no advantages over day 3 transfer regarding the
clinical PR, IR, the ongoing PR, & does not diminish the incidence
of multiple pregnancies
(Sallam et al, 2003; meta-analysis).
Little difference in the major outcome parameters between early
ETand blastocyst culture
(Blake et al, 2004, Chocrane library).
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4. Cervical infection:
Cervical infection diminishes the P & IRs significantly. The clinical
PR for patients with positive cultures was 21% compared to
38.4% for patients with negative cultures
(Sallam et al , 2003; meta-analysis)
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5. Use of antibiotics:
The prescription of antibiotics from the day of ovum pick-
up up to 6 days (Amoxicillin + Clauvulanic acid) does not
improve the implantation rate
(Peikrishvili et al, 2004).
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6. The use of fibrin sealant:
With the use of fibrin sealant ectopic pregnancy may be
completely avoided
(Felchtinger et al,1992).
On the other hand,
Ben-Rafael et al (1995) found that use of fibrin sealant for ET
is advantageous only in elderly women (aged 39-42 years),
but has no apparent effect on the success rate or ectopic
pregnancy in younger patients.
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7. The ET medium:
It has been suggested that the existence of hyaluronon in the
culture media prior to ET may increase the PR. Embryo Glue
medium is an ET medium containing high amount of hyaluronon.
Embryo glue has no benefit on I or PRs
(Karimian et al, 2004; Enginsu et al, 2004; Mardesic et al, 2004)
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8. The volume of fluid applied with embryos in ET
IR is significantly lower for low volumes of fluid
applied with embryo in ET (below 3.2 ul in the fluid
applied before embryo & below 2.2 ul in the fluid
around embryo)
(Rezabek et al, 2004)
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9. Bladder filling:
No significant differences in difficulties encountered at ET
or in the chance of pregnancy were found in women with
& without a filled bladder
(Mitchell et al, 1989)
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10. Vigorous flushing of the cervical canal with culture
medium before ET
do not improve the clinical pregnancy rates
(Sallam et al, 2000).
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11. Type of ET catheter:
a. The Frydman catheter yielded the highest PRs (32%
/ET).
b. The Wallace catheter showed PR of 19% /ET, while
the TDT catheter yielded the lowest PR (9% /ET)
(Wisanto et al, 1989)
c. The choice of catheter (Wallace or Erlangen metal
catheter) did not affect PR
(Ghazzawi et al, 1999)
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d. PR was significantly higher in K-soft 5000 than the TDT
catheter
(van Weering,2002).
e. PRs were similar when the Wallace or the Cook catheter was
used
(Karande et al,2002; Saldeen et al, 2003; Mcllveen et al,
2004)
f. 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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12. Transmyometrial Vs transcervical ET:
No benefit was derived by electing transmyometrial ET in
preference to tramscervical ET in patients who had failed to
conceive in previous cycles
(Groutz et al,1997).
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1. Ultrasound-guided ET:
UGET is associated with an increase in the clinical P & 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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Laminar flow of transfer medium (jet phenomenon)
detected during UGET correlates with significantly improved PRs
over non-laminar flow
(Cruickshank et al, 2003).
Non-laminar flow
may be visualizing obstructed flow, possibly related to the
catheter tip abutting on the endometrium.
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2. Site of embryo deposition
IR was significantly higher IR when the embryos were deposited
2 cm below the uterine fundus compared to when deposited 1 cm
below the fundus
(Coroleu et al ,2002).
The mid-cavity technique is superior to deep-cavity because of a
lower percentage of ectopic pregnancies
(Nazari et al, 1993).
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3. Difficult ET:
Difficult ET diminish the P & IR significantly
(Meata-analysis, Sallam et al, 2003).
The clinical PR for patients with difficult transfers was
22.3% compared to 31% for patients with easy transfers.
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4. Hypnosis:
Guided relaxation hypnosis does not change the results
of ET with IVF
(Rezabek et al, 2003)
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1. Slow withdrawal of the ET catheter.
No statistically significant difference in the PR between
slow withdrawal of the catheter immediately after embryo
deposition & a 30 second delay before catheter
withdrawal
(Martinz et al, 2001)
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2. Mechanical pressure on the portiovaginalis of the cervix:
Applying gentle mechanical pressure on the portiovaginalis of the
cervix using the vaginal speculum during & after transferring the
embryo significantly improved the clinical P & IR
(Mansour, 2004).
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3. Bed rest:
A 24 h period of bed rest following ET is not associated
with a better outcome when compared with a 20 min rest
period
(Botta & Grudzinskas,1997).
Prolonged bed rest does not influence the IR.
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4. Sexual intercourse around time of ET
No significant difference between the intercourse and
abstain groups in relation to the PR (23.6 Vs 21.2%),
but the proportion of transferred embryos that were
viable at 6-8 weeks was significantly higher in women
exposed to semen compared to those who abstained
(11 Vs 7.7%)
(Tremellen et al,2001).
Hence exposure to semen around the time of ET
increases the likelihood of successful early embryo
implantation and development.
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Pregnancy rates are significantly increased when
1. Trial transfer
2. Soft ET catheter
3. Ultrasound-guided ET
4. Deposition of the embryo 2 cm below the uterine
fundus.
5. Mechanical pressure on the portiovaginalis of the
cervix
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