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unpublished sources) &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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