1. Benha University Hospital,Egypt Delta (Mansura) & Benha Fertility Centers Email: elnashar1953@yahoo.com

2. Embryo transfer (ET) is 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.

3. Our objective To review RCT & meta- analyses concerning the factors affecting the success of ET.

4. Materials & methods An electronic search of the Chocrane library & Pub Med for RCT & meta- anylysis concerning ET from 1990 to 2004.

5. The Cochrane Collaboration Library is 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

6. 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

7. RCT is the gold standard in clinical research. RCT is the standard method for answering questions about the effectiveness of different therapies RCT provides the strongest evidence for the cause & effect relationship & is subject to the least amount of bias.

8. 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evidence pertaining to a particular field of research has been collected (via a systematic search of the literature & unpublished sources) & evaluated using predefined quality criteria.

9. Meta-analysis Systematic reviews in which the numerical results of different studies have been combined using standard statistical techniques.

10. 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.

12. 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.

13. 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

14. 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).

15. 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).

16. 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)

17. 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).

18. 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.

19. 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)

20. 8. The volume of fluid applied with embryos in ET Rezabek et al (2004) found significantly lower IR 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)

21. 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)

22. 10. Vigorous flushing of the cervical canal with culture medium before ET do not improve the clinical pregnancy rates (Sallam et al, 2000 ).

23. 11. Type of ET catheter: a. The Frydman catheter yielded the highest PRs (32% /ET). The Wallace catheter showed PR of 19% /ET, while the TDT catheter yielded the lowest PR (9% /ET) (Wisanto et al, 1989) b. The choice of catheter (Wallace or Erlangen metal catheter) did not affect PR (Ghazzawi et al, 1999)

24. c. PR was significantly higher in K-soft 5000 than the TDT catheter (van Weering,2002). d. PRs were similar when the Wallace or the Cook catheter was used (Karande et al,2002; Saldeen et al, 2003; Mcllveen et al, 2004) e. PR was increased by 50% when the soft double lumen catheter rather than the single lumen catheter was used (McDonald & Norman,2002).

25. 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).

27. 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

28. 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.

29. 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).

30. 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.

31. 4. Hypnosis: Guided relaxation hypnosis does not change the results of ET with IVF (Rezabek et al, 2003)

33. 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)

34. 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).

35. 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.

36. 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.

38. 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

39. Benha University Hospital,Egypt Delta (Mansura) & Benha Fertility Centers Email: elnashar1953@yahoo.com