ultrasound guidaed embryo transfer

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DEBATE

Embryo transfer: does ultrasound guidance makea difference?

Comment by: Mohamed Yehia, MD., FRCOG

Cairo, Egypt

Ever since the birth of the first in-vitro

fertilization (IVF) baby in 1978 (1), the

advancement in ovulation stimulation regimes,

oocyte collection and culture mediums has been

phenomenal. However, the technique of uterine

embryo transfer remains largely unchanged, since

it was first described. The vast majority of

transferred embryos fails to implant in spite of

improvements in ovulation induction, fertilization

and embryo cleavage. On average, up to 90% of

apparently healthy zygotes transferred in utero aredestined to vanish, giving no signs of trophoblastic

attachment and production of human chorionic

gonadotrophin (HCG) (2).

Though factors relating to the embryo itself

(quality, aneuploidy etc), hostile uterine

environment (e.g. reflux of hydrosalpinx),

inadequate endometrial development or uterine

cavity anomalies and uterine contractions

contribute to this failure, definitely the technique

itself contributes to loss of some potentially

favorable embryos for implantation.

The wide variability between clinicians workingin the same center (which to an extent nullifies the

potential difference in the laboratory circumstances)

clearly demonstrates the role of the clinician in

embryo transfer and the magnitude of problem.

The technique of embryo transfer that was used

for long time was the clinical touch. It simply

means that you feel the internal os and then either

you advance the catheter till the fundus is felt and

withdraw the catheter for 1 or 2 cm and position

the embryos. Alternatively the clinician advances

the inner catheter after feeling the resistance of the

internal os by 3-4 cm based on previousmeasurement of the uterine cavity, Woolcott and

Stanger studied 121 consecutive transvaginal

ultrasound-guided embryo transfers (3).

Observation was made of the guiding cannula and

transfer catheter placement in relation to the

endometrial surface and uterine fundus during

embryo transfer. They concluded that tactile

assessment of embryo transfer catheter placement

was unreliable since, in 17.4% of transfers, the

outer guiding catheter inadvertently abutted the

fundal endometrium, the outer guiding cannula

indented the endometrium in 24.8% and thetransfer catheter embedded in the endometrium in

33.1%. Unavoidable sub-endometrial transfers

occurred in 22.3% and avoided accidental tubal

transfer in 7.4%.

The possible use of US guidance to facilitate

embryo transfer was first reported by Strickler et al

(4), and shortly afterwards by Leong et al., (5).

However the technique did not gain popularity till

the last few years where several reports have

claimed improved pregnancy rate after adoption of

ultrasound guided transfer (6, 7).

This article will try to debate the following points:

1. Does ultrasound guided transfer improvepregnancy rate?

2. Does it make the procedure easier?3. Which route abdominal, rectal or vaginal

ultrasound is better?

4. Where to place the embryos?5. 2D versus 3-D in ultrasound embryo transfer6. Which catheter?

Middle East Fertility Society Journal Vol. 11, No. 3, 2006Copyright Middle East Fertility Society

Vol. 11, No. 3, 2006 Debate ET: does ultrasound guidance make a difference? 173


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1. Does ultrasound guided embryo transfer

increase pregnancy rate?

The reports regarding the effect of guiding the

transferred embryo deposition by ultrasound are

conflicting. In a prospective study using abdominal

ultrasound (8), it was found that there was no

significant effect of ultrasound on pregnancy

outcome. In a large prospective study comparing

clinical and ultrasound-guided embryo transfer (9),

there was still no significant improvement seen in

either pregnancy or implantation rates. Two studies

demonstrated significant differences between the

clinical touch method and transabdominal

ultrasound-guided embryo transfer, retrospectively

(7) and prospectively (10) followed. To confusethe situation more, a study by Prapas et al. (11)

found that ultrasound guided embryo transfer

increases pregnancy rate at day 3or 4 but not if the

transfer occurs at day 5. In a recent study Bedawy

et at (12) could not demonstrate significant

increase in pregnancy rate if an experienced

operator performed the procedure with or without

ultrasound. A meta-analysis by Buckett et al (13)

concluded that Ultrasound-guided embryo transfer

significantly increases the chance of clinical

pregnancy and significantly increases the embryo

implantation rate.

2. Does it make the procedure easier?

It is generally accepted that an atraumatic embryo

transfer is essential for successful implantation

(14-16). Mansour et al. (17) found that Dummy

embryo transfer: a technique that minimizes the

problems of embryo transfer and improves the

pregnancy rate in human in vitro fertilization.

Frequency of embryo transfers reported as difficult

differs widely. In a series of 876 embryo transfer

procedures, 1.3% were impossible, 3.2% verydifficult and 5.6% difficult (15). In more recent

surveys, while some authors refer to 2-3% of

difficult transfers (10), others have reported rates

of 14% (18) and 19% (6). Coroleu et al. did not

observe significant differences in the difficulty of

the procedure between US-guided and clinical

touch transfer, (10). Kan et al. reported no

differences in the difficulty of transfers, but they

excluded from their study patients in whom a

difficult transfer was anticipated. On the other

hand, they had a relatively high frequency of

difficult transfers in both populations (10-11%)

(9). In a retrospective report, whereas no

significant differences were found in the difficulty

of embryo transfer, it was reported that when the

uterus was acutely anteflexed, the subjective

feeling was that US-guided embryo transfer was

easier and followed a straighter course by filling

the bladder (7). Matorras et al. (19) in a

prospective study found that ultrasound abdominal

embryo transfer had significantly decreased the

number of difficult transfer. Sallam et al. (20) in a

trial to increase the percentage of easy transfer

tried to measure the uterovesical angle and mould

the catheter before insertion into the cavity andfound that this procedure increase the proportion of

easy embryo transfer.

3. Which ultrasound route is better?

The majority of the published studies were done

with abdominal ultrasound. Sallam et al. (7-10, 19,

20). The value of abdominal ultrasound in addition

of visualizing the catheter is to straighten the

uterovesical angle which my make the insertion of

the catheter easier. Kojima et al. (21) tried to usevaginal ultrasound as it allows visualization of the

tip of the catheter precisely and concluded that it

increases the pregnancy and implantation rate; in

the same time they admitted that it technically

more difficult. The procedure did not gain

popularity because of it's discomfort to the patient.

Isobe et al. (22) compared the transrectal approach

in retroflexed uterus and found that it increases the

incidence of easier transfer and pregnancy rate;

however, there was no comment on the acceptance

of the procedure.

4. Where to place the embryos?

While it has been traditionally accepted that the

embryos should be placed ~10 mm below the

fundal endometrial surface (23, 24), some authors

have suggested that placing embryos rather lower

in the uterine cavity may improve pregnancy rates

(24-26). Finally, other reports have indicated that

the depth of the replacement has no influence on

174 Debate ET: does ultrasound guidance make a difference? MEFSJ


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the implantation rate provided that the transfer is in

the upper half of the uterine cavity (8, 27, 28).

Coroleu et al. (29) found that embryos should be

replaced 15-20 mm from the fundus endometrial

surface rather than performing high fundal

placement in order to improve implantation rates.

Pop et al. (30) found that for every additional

millimeter embryos are deposited away from the

fundus, the odds of clinical pregnancy increased by

11%.

5. 2D versus 3D in ultrasound embryo transfer

Baba et al. (31) examined the feasibility of using

three-dimensional (3D) ultrasound (US) guidance

in routine embryo transfer (ET) procedures.Seventy-five ETs were performed using a 3D US

scanner to locate the catheter tip in the uterine

cavity. Three-dimensional ultrasound could show

the exact position of the tip of the catheter in the

uterine cavity quickly enough in most cases. They

concluded that it should be used in ET for seeking

an optimal transfer area in the uterine cavity to

assist in achieving high success rates and less

complications.

6. Which catheter?

Coroleu et al. (32) In a pilot study suggested that

the use of the echogenic Wallace catheter

simplifies ultrasound-guided embryo transfer as it

facilitates catheter identification under ultrasound,

and thus the duration of the embryo transfer

procedure was significantly shorter in the

echogenic catheter group as compared with the

standard catheter group. However, they could not

find a definite benefit in terms of pregnancy rates.

In contrast, the use of the new catheter was

associated with a significant increase in the

number of twin pregnancies.

CONCLUSION

Traditionally, embryo transfer has been performed

blindly. Any additional means to ensure the proper

deposition of the transferred embryos should be

welcomed .The use of abdominal ultrasound seems

to offer better pregnancy rate in most of the

published reports particularly for junior,

inexperienced clinicians. It also appears that

ultrasound guided transfer can ensure the exact

position of embryo deposition. If larger studies

confirm that deposition in the mid or lower cavity

increases pregnancy rate, then ultrasound would be

invaluable in embryo transfer. The newly marketed

echo dense catheters needs to be evaluated more to

prove it facilitates recognition of the tip position.

REFERNCES

1. Edwards RG, Steptoe PC and Purdy JM. Establishing full-term human pregnancies using cleaving embryos grown in

vitro. Br J Obstet Gynaecol 1980; 87: 737756.

2. Nikas G, Develioglu OH, Toner JT. et al. Endometrialpinopodes indicate a shift in the window of receptivity in

IVF cycles. Hum Reprod 1999; 14:787-792.

3. Woolcott R and Stanger J. Potentially important variablesidentified by transvaginal ultrasound-guided embryo

transfer. Hum Reprod 1997; 12:963-966.

4. Strickler RC, Christianson C, Crane JP. et al. Ultrasoundguidance for human embryo transfer. Fertil Steril 2003; 43:

54-61.

5. Leong M, Leung C, Tucker M, Wong C and Chan H.Ultrasound-assisted embryo transfer. J In vitro Fertil Embryo

Transfer 1986; 3: 383-385.

6. Lindheim SR, Cohen MA and Sauer MV. Ultrasound guidedembryo transfer significantly improves pregnancy rates in

women undergoing oocyte donation. Int J Gynaecol Obstet1999; 66: 281-284.

7. Wood EG, Batzer FR, Go KJ, Gutmann JN and Corson SL.Ultrasound-guided soft catheter embryo transfers will

improve pregnancy rates in in-vitro fertilization. Hum

Reprod 2000; 15: 107-112.

8. Al-Shawaf T, Dave R, Harper J. et al. Transfer of embryosinto the uterus: how much do technical factors affect

pregnancy rates? J. Assist. Reprod. Genet. 1993; 10: 31-36.

9. Kan AKS, Abdalla HI, Gafar AH et al. Embryo transfer:ultrasound-guided versus clinical touch. Hum Reprod 1999;

14: 1259-1261.

10. Coroleu B, Carreras O, Veiga A. et al. Embryo transferunder ultrasound guidance improves pregnancy rates after

in-vitro fertilization. Hum Reprod 2000; 15: 616-620.11. Prapas Y, Prapas N, Hatziparasidou A, Vanderzwalmen P,

Nijs M, Prapa S and Vlassis G. Ultrasound-guided embryo

transfer maximizes the IVF results on day 3 and day 4

embryo transfer but has no impact on day 5. Hum Reprod

2001; 16: 1904-1908.

12. Bedaiway M. Evaluation of the effect of the adoption ofultrasound guidance for embryo replacement on the

pregnancy outcome for multiple providers. Middle East

Fertil Soc J Vol. 2006; 11(2):127-134.

13. Buckett William M. A meta-analysis of ultrasound-guidedversus clinical touch embryo transfer. Fertil

Steril. 2003; 80:1037-1041



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14. Leeton J, Trounson A, Jessup D and Wood C. The techniquefor human embryo transfer. Fertil Steril 1982; 38: 156-161.

15. Wood C, McMaster R, Rennie G, Trounson A and Leeton J.Factors influencing pregnancy rates following in vitro

fertilization and embryo transfer. Fertil Steril 1985; 43: 245-250.

16. Diedrich K, Van der Ven H, Al-Hasani S and Krebs D.Establishment of pregnancy related to embryo transfer

techniques after in-vitro fertilization. Hum Reprod 1989; 4

(Suppl.): 111-114.

17. Mansour R, Aboulghar M and Serour G. Dummy embryotransfer: a technique that minimizes the problems of embryo

transfer and improves the pregnancy rate in human in vitro

fertilization. Fertil Steril 1990; 54: 678-681.

18. Tur-Kaspa I, Yuval Y, Bider D, Levron J, Shulman A andDor J. Difficult or repeated sequential embryo transfers do

not adversely affect in-vitro fertilization pregnancy rates or

outcome. Hum Reprod 1998; 13: 2452-2455.

19. Matorras R, Urquijo E, Mendoza R, Corcstegui B, ExpsitoA, and Rodrguez-Escudero FJ. Ultrasound-guided embryotransfer improves pregnancy rates and increases the

frequency of easy transfers. Hum Reprod 2002; 17: 1762 -

1766.

20. Sallam H. Agameya A, Rahman A, Ezzeldin F, and SallamA. Ultrasound measurement of the uterocervical angle before

embryo transfer: a prospective controlled study. Hum

Reprod 2002; 17: 1767 - 1772.

21. Kojima K, Nomiyama M, Kumamoto T, Matsumoto Y, andIwasaka T. Transvaginal ultrasound-guided embryo transfer

improves pregnancy and implantation rates after IVF. Hum

Reprod 2001; 16: 2578 - 2582.

22. Isobe T, Minoura H, Kawato H and Toyoda N. Validity of

trans-rectal ultrasound-guided embryo transfer againstretroflexed uterus Reprod Med Biol 2003; 2: 159163.

23. Webster J. Embryo replacement. In Fishel, S. and Symonds,E.M.(eds) In Vitro Fertilisation: Past, Present and Future.

IRL Press, Oxford, 1986; pp. 127-134.

24. Brinsden PR. Oocyte recovery and embryo transfer. InBrinsden, P.R. (ed.) Textbook of In Vitro Fertilization and

Assisted Reproduction, 2ndedn. Parthenon, London,

1999pp.171-184.

25. Waterstone J, Curson R and Parson. Embryo transfer to lowuterine cavity. Lancet 1991; 337: 1413.

26. Naaktgeboren N, Broers FC, Heijnsbrock I. et al. Hard tobelieve, hardly discussed, nevertheless very important for the

IVF/ICSI results; embryo transfer technique can double or

halve the pregnancy rate. Hum Reprod 1997; 12: 1188-119027. Nazari A, Askari HA, Check JH. et al. Embryo transfertechnique as a cause of ectopic pregnancy in in-vitro

fertilization. Fertil Steril 1993; 60: 919-921.

28. Roselund B, Sjoblom P and Hillensjo T. Pregnancyoutcome related to the site of embryo deposition in the

uterus. J Assist Reprod Genet 1996; 13: 511-513.

29. Coroleu B, Barri PN, Carreras O, Martnez F, Parriego M,Hereter L, Parera N, Veiga Balasch AJ. The influence of the

depth of embryo replacement into the uterine cavity on

implantation rates after IVF: a controlled, ultrasound-guided

study. Hum Reprod 2002; 17(2): 341-346

30. Pope CS, Cook EK, Arny M, Novak A, Grow DR. Influenceof embryo transfer depth on in vitro fertilization and embryo

transfer outcomes. Fertil Steril 2004;81(1):51-8.

31. Baba K, Ishihara O, Hayashi N, Saitoh M, J. Taya J and.

Kinoshita K. Three-dimensional ultrasound in embryotransfer. Ultrasound in Obstetrics & Gynecology 2000;16:

372 .

32. Coroleu B, Barri P, Carreras O, Belil I, Buxaderas R, VeigaA, and BalaschJ. Effect of using an echogenic catheter for

ultrasound-guided embryo transfer in an IVF programme: a

prospective, randomized, controlled study Hum Reprod

2006; 21: 1809 - 1815.

Mohamed Yehia MD FRCOG

Professor of Obstetrics & Gynecology

Ain Shams UniversityCairo Egypt.

Comment by: Ahmed Abou-Setta, M.D.Cairo, Egypt

Despite the major advancements made in

ovarian controlled hyperstimulation protocols and

in vitro embryo development, over the years the

pregnancy and embryo implantation rates

following embryo transfer have remained

relatively low, and to some extend plateau (1).

Attempts at improvement have come about by

scrutinizing every aspect of the in vitro fertilization(IVF) procedure, especially analysis of different

patient populations, choice of stimulation

protocols, culture techniques, and embryo selection

guidelines. Even so, the standard embryo transfer

technique has relatively been unmodified.

Due to its seemingly simple nature by

comparison with the complicated processes of

ovarian stimulation, gonadotrophin releasing

hormone (GnRH) analogue administration, oocyte

retrieval or methods for embryo culture, this innate

process of returning the newly created embryos

back into the recipient uterus has received little

recognition as a decisive step in the success of the

IVF procedure.

In general, the pregnancy rate following

embryo transfer has been shown to be dependent

upon multiple factors including embryo quality,

endometrial receptivity and the technique of the

embryo transfer itself (2). The aim of the embryo

transfer procedure is to atraumatically and

accurately place embryos within the uterus; in order



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Study US-guided Clinical Touch OR (fixed) OR (fixed)

or sub-category n/N n/N 95% CI 95% CI

01 Proper randomization

Matorras 2002 56/255 36/260 1.75 [1.11, 2.77]

deCamargoMartins2004 20/50 13/50 1.90 [0.81, 4.43]Subtotal (95% CI) 305 310 1.78 [1.19, 2.67]

Total events: 76 (US-guided), 49 (Clinical Touch)

Test for heterogeneity: Chi = 0.03, df = 1 (P = 0.87), I = 0%

Test for overall effect: Z = 2.80 (P = 0.005)

02 Quasi or unkown method of randomization

Subtotal (95% CI) 0 0 Not estimable


Test for heterogeneity: not applicable

Test for overall effect: not applicable

Total (95% CI) 305 310 1.78 [1.19, 2.67]


Test for heterogeneity: Chi = 0.03, df = 1 (P = 0.87), I = 0%


0.1 0.2 0.5 1 2 5 10

Favours Clinical Favours US-guided

Figure 1. Meta-analysis forest plots showing live-birth rate following US-guided versus clinical touch embryo transfer. "Reprinted

from Fertility and Sterility, with permission from the American Society for Reproductive Medicine."

to allow for proper implantation and fetal

development.

In a recent awakening, clinicians are beginning

to realize the full extent of this highly delicate

procedure on the success rates. In a wave of

publications, different factors that constitute the

embryo transfer technique as a whole have begunto be tested and analyzed. Factors as ease of the

procedure, catheter choice, and dummy embryo

transfer, among others, have proven to improve the

clinical outcomes.

Today, more than twenty-years since the first

reports of the beneficial effect of ultrasound

guidance during the blind embryo transfer

procedure were published (3, 4), the routine use of

ultrasonography to guide the intrauterine embryo

transfer catheter placement are still highly debated.

This has been fueled by the conflicting results of

published clinical trials, with some concluding that

ultrasound guidance improves the clinical

pregnancy, and implantation rates, while others

reporting no such improvement in their results.

In light of this controversy several systematic

reviews of the evidence have been performed to

determine the possible beneficial effect of this

adjunctive technique. This is of importance since

systematic reviews and meta-analyses of

randomized controlled trials have proven to be the

highest level of evidence in the hierarchy of

medical knowledge.

The first reports were performed by Sallam et

al. (5) and Buckett (6). Both demonstrated that the

use of ultrasonography was a beneficial tool during

the embryo transfer procedure by increasing the

clinical pregnancy rates.In addition, a recent systematic review and

meta-analysis of randomized trials demonstrated

that the patients undergoing embryo transfer under

ultrasound-guidance has a significantly higher

likelihood of achieving a live birth, ongoing

pregnancy and clinical pregnancy than patients

undergoing the standard clinical touch embryo

transfer (7). Moreover, subgroup analyses of only

the properly randomized trials, fresh non-donor

cycles, and the frozen embryo replacement cycles

revealed similar results (Figure 1, 2, 3).

It is also important to note that to date all the

published randomized trials regarding ultrasound

guidance during embryo transfer have examined

the role of 2-Dimensional (2D) trans-abdominal

ultrasound guidance. Even so, vaginal ultrasound-

guided embryo transfer (8), as well as the use of

three-dimensional (3D) (9) and fourth-dimensional

(4D) ultrasound-guided embryo transfer have been

reported in observational and non-randomized

trials.



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Figure 2. Meta-analysis forest plots showing ongoing pregnancy rate following US-guided versus clinical touchembryo transfer."Reprinted from Fertility and Sterility, with permission from the American Society for Reproductive Medicine."

The exact mechanism whereby ultrasound-

guided embryo transfer improves pregnancy rates

and embryo implantation remains unclear. Several

theories have been proposed to identify the

mechanisms whereby the transfer technique is

optimized. These include confirming the position

of the tip of the embryo transfer catheter within the

uterine cavity, the site of embryo deposition,

increasing the frequency of easy embryo

transfers, and avoiding endometrial indentation.

Nevertheless, some clinicians argue that the real

benefit of ultrasound guidance lies is the ability ofincreasing the clinical appreciation of the pelvic

anatomy during transfer. They infer that

ultrasound guidance, compared with the standard

clinical touch alone, will not significantly increase

the pregnancy rates when embryo transfer is

performed by experienced professionals. Even so,

this simple modification will allow for

standardization of the transfer technique and

therefore decrease any unexpected variation in

pregnancy rates among different clinicians in the

same center.

Whatever the underlying mechanism, the

overall conclusion is that ultrasound-guided

embryo transfer is significantly more effective than

embryo transfer by clinical touch alone. It is hoped

that this evidence will be quickly translated from

the medical literature to everyday clinical practice.

REFERENCES

1. Edwards RG. Clinical approaches to increasing uterinereceptivity during human implantation. Hum Reprod.

1995 Dec;10 Suppl 2:60-6.

2. Mansour RT, Aboulghar MA. Optimizing the embryotransfer technique. Hum Reprod. 2002 May;17(5):1149-

53.

3. Strickler RC, Christianson C, Crane JP, Curato A,Knight AB, Yang V. Ultrasound guidance for human

embryo transfer. Fertil Steril. 1985 Jan;43(1):54-61.




Coroleu 2000 85/182 52/180 2.16 [1.40, 3.33]

Tang 2001 94/400 76/400 1.31 [0.93, 1.84]Coroleu 2002 25/93 14/91 2.02 [0.97, 4.20]

Garcia-Velasco 2002 100/187 89/187 1.27 [0.84, 1.90]

Matorras 2002 57/255 37/260 1.74 [1.10, 2.74]

deCamargoMartins2004 20/50 13/50 1.90 [0.81, 4.43]

Kosmas 2006 31/101 32/95 0.87 [0.48, 1.59]

Subtotal (95% CI) 1268 1263 1.49 [1.25, 1.78]


Test for heterogeneity: Chi = 8.44, df = 6 (P = 0.21), I = 28.9%

Test for overall effect: Z = 4.38 (P < 0.0001)


Prapas 2001 187/433 204/636 1.61 [1.25, 2.07]

Marconi 2003 21/41 12/42 2.63 [1.06, 6.50]

Weissman 2003 36/160 28/124 1.00 [0.57, 1.74]

Subtotal (95% CI) 634 802 1.54 [1.23, 1.92]




Total (95% CI) 1902 2065 1.51 [1.31, 1.74]




0.1 0.2 0.5 1 2 5 10




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Wisanto 1989 19/100 9/100 2.37 [1.02, 5.54]

Coroleu 2000 91/182 61/180 1.95 [1.28, 2.98]

Tang 2001 104/400 90/400 1.21 [0.88, 1.67]

Coroleu 2002 32/93 18/91 2.13 [1.09, 4.16]

Garcia-Velasco 2002 112/187 103/187 1.22 [0.81, 1.84]

Matorras 2002 67/255 47/260 1.62 [1.06, 2.46]

deCamargoMartins2004 21/50 15/50 1.69 [0.74, 3.86]

Kosmas 2006 53/101 50/95 0.99 [0.57, 1.74]

Subtotal (95% CI) 1368 1363 1.46 [1.23, 1.72]





Al-Shawaf 1993 44/152 27/89 0.94 [0.53, 1.66]

Prapas 1995 22/61 16/71 1.94 [0.90, 4.16]

Kan 1999 37/98 28/97 1.49 [0.82, 2.72]

Abdelmassih 2001 10/19 6/20 2.59 [0.70, 9.64]

Prapas 2001 206/433 229/636 1.61 [1.26, 2.07]

Sallam 2002 84/320 59/320 1.57 [1.08, 2.29]

Bar Harva 2003 22/65 15/66 1.74 [0.80, 3.76]

Marconi 2003 25/41 15/42 2.81 [1.15, 6.85]

Weissman 2003 45/160 35/124 1.00 [0.59, 1.68]

Moraga-Sanchez 2004 21/33 13/34 2.83 [1.05, 7.61]

Li 200566/178 38/152 1.77 [1.10, 2.85]

Maldonado 2005 5/13 10/13 0.19 [0.03, 1.03]

Subtotal (95% CI) 1573 1664 1.53 [1.32, 1.78]




Total (95% CI) 2941 3027 1.50 [1.34, 1.67]




0.1 0.2 0.5 1 2 5 10


Figure 3. Meta-analysis forest plots showing clinical pregnancy rate following US-guided versus clinical touch embryo transfer.

"Reprinted from Fertility and Sterility, with permission from the American Society for Reproductive Medicine."

4. Sallam HN and Sadek SS. Ultrasound-guided embryotransfer: a meta-analysis of randomized controlled trials.

Fertil Steril. 2003 Oct; 80(4):1042-6.

5. Buckett WM. A meta-analysis of ultrasound-guidedversus clinical touch embryo transfer. Fertil Steril. 2003

Oct;80(4):1037-41.

6. Abou-Setta AM, Mansour RT, Al-Inany HG et al. 2007Among women undergoing embryo transfer, is the

probability of pregnancy and live birth improved with

ultrasound-guidance than with clinical touch alone? A

systemic review and meta-analysis of prospective

randomized trials. Fertil. Steril. (in press).7. Kojima K, Nomiyama M, Kumamoto T, Matsumoto Y,Iwasaka T. Transvaginal ultrasound-guided embryo

transfer improves pregnancy and implantation rates

after IVF. Hum Reprod. 2001;16:2578-2582.

8. Baba K, Ishihara O, Hayashi N, Saitoh M, Taya J,Kinoshita K. Three-dimensional ultrasound in embryo

transfer. Ultrasound Obstet Gynecol. 2000;16:372-373.

Ahmed Abou-Setta, M.D.

Comment by: Mohamed A. Bedaiwy, M.D.Ohio, USA

Despite its obvious simplicity compared to

other steps in any given IVF-ET cycle, embryo

transfer is probably the most critical one

influencing the cycle outcome. Little and probably

late attention has been paid to the role of ET

methodology and its overall impact on successrates. Of all factors influencing the ET process,

ultrasound guidance of the ET has been studied the

most over the past decade. Issues related to the ET

technique, ET provider/physician, transferred

embryos and unloading site in the uterus and their

relationship to ultrasound guidance were the most

debatable aspects of the process. Of all

confounding variables, the following controversial

issues will be discussed.



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1. Ultrasound guidance: is evidence a must?

Three approaches have been adopted for

embryo transfer. The first approach used was a

fundus-contact approach also called blind-ET

whereby the transfer catheter was advanced to the

uterine fundus, then withdrawing the catheter 510

mm and unloading the embryos into the uterine

cavity. Simply it is a contact the fundus-withdraw-

unload method. This approach was quickly

abandoned because it provokes bleeding and

initiates uterine contractions which in-turn will

jeopardize the cycle outcome. The second

approach was an atraumatic one commonly known

as clinical touch transfer. It simply entails all

techniques in which ultrasound is not performed,but contact with the fundus is avoided. Finally, any

ET approach in which we use ultrasound guidance

is called US-guided ET. Consequently US

guidance is a way to monitor the transfer step

whether we touch the fundus or not. Indeed it

could be beneficial if executed atraumatically,

however it might not be as helpful and even

implying false-sense of security if the fundus is

touched or frequent to-and fro- movements of the

catheter at the time of the transfer were

experienced. Practically speaking ET techniques

come down to 2 methods; fundus contact methodand non-contact method whether we use ultrasound

or not.

Although many studies found no extra

advantage for the use of abdominal US

ultrasonography in ET (1, 2), its use was associated

with easier transfers (3) less use of tenaculum and

less incidence of blood contaminated catheters (4).

Moreover it gives a sensation of comfort to both

the patient and the physician by observing the air

bubble and assuring that the embryos remain in the

cavity.

The results of two recent meta-analyses ofprospective, randomized comparisons (5, 6)

strongly promoted the use of US guidance to

improve the results. However, differences in study

design and execution may limit the statistical value

by overstating the effect of ultrasonography and

underestimating the important differences in study

design. For instance the meta-analysis by Buckett

demonstrated that none of the prospective

randomized studies included has enough power to

detect a 5% difference in clinical pregnancy rates.

The clinical touch method depends very much on

the experience of the performer thus it will give

inconsistent results in different hands. It was found

that when the uterine length was ultrasonographically

measured before ET, the results were comparable to

those of ultrasonographically performed ET (7).

Consequently, ultrasound guidance may improve

outcome when endometrial cavity length has not

been previously accurately measured, but when it has

been reliably performed, ultrasound guidance may

have no effect. In many programs with high

pregnancy rates including ours, adoption of US-

guided ET has not been shown to have a significant

effect on outcome measures (8). Obviously, there is

lack of evidence to justify the routine use of USguidance during ET. However, in 2003 Smith and

Pell published an impressive article titled:

"Parachute use to prevent death and major trauma

due to gravitational challenge (9). They used the

lack of randomized controlled trials in testing

parachutes to show that situations still exist where

such trials are unnecessary. The use of simple step

as US guided-ET could be used to justify their

cause!

2. Does the adoption of ultrasound guidance

improve the providers own performance?

The impact of ultrasound guidance on the

pregnancy rate per provider (before and after the

adoption of ultrasound guidance) was recently

evaluated by our group. We found that US

guidance did not reduce the time of the ET

procedure. In addition, it did not reduce the

percentage of bloody catheters at the end of the

procedure. More importantly, no statistical

difference was seen in the presence or number of

gestational sacs following embryo transfer either

before or after the adoption of the transabdominalultrasound guidance for 3 equally experienced

providers (8).

3. Which ultrasound? Transvaginal (TVUS) or

transabdominal (TAUS)? 2D, 3D or 4D?

One limitation of TAUS is the need to be

performed with a full bladder and a sonographer

should be present at the time of the procedure. This



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in turn can lead to the discomfort of the patient and

her anxiety to empty it shortly after the procedure.

Moreover in cases of obesity or retroversion,

TAUS is not ideal. However, performing TAUS

with a full bladder helps in straightening the

uterocervical angle facilitating the procedure. It

was claimed that TVUS allows more precise

embryo placement than the TAUS since the

catheter tip could be better delineated. Also it

probably minimize endometrial trauma as it gives

clear fine images of the uterine flexion and the

endometrial midline curve, compared to TAUS

(10). However, TAUS is the approach adopted by

the majority of IVF programs.

With the recent advances in acoustic imaging,

the application of 3-dimensional, or 4-D (real-time 3-dimensional) ultrasonography to ET might

be helpful in many ways. The 3D US allows

viewing the catheter tip in a frontal as well as a

sagittal and transverse plans, thus it facilitates

precise embryo placement inside the uterus.

However, it does not seem to be vital in

maximizing the success rate at the current time.

Given the limitation of the currently available 2D

machines in monitoring embryo migration after

transfer, 3-D ultrasonography could prove

beneficial in this regard as embryos may be

propelled by uterine contractions to otherlocations, including out of the cavity at the end of

ET. Despite the growing interest in adopting this

new technology, it should improve catheter

placement, pregnancy rates, and nullify ectopic

pregnancy to be justifiable.

4. What does ultrasound guidance actually

guide?

Ideally ultrasound should guide catheter

placement, unloading of embryos and catheter

withdrawal. The primary of focus of the vastmajorities of the current studies dealt with the issue

of US-ET was on accurate placement of the

catheter near the optimal target site. The optimal

site of transfer, which most probably represents an

area rather than a single point, is yet to be

identified. US may confirm the location of the

catheter inside the uterus, however, it may not

facilitate catheter entry particularly with tortuous

cervical canal of acute cervico-uterine angle. Due

to the limited acoustic window if any given

transducer, it might not be possible to show the

entire length of the catheter along its path.

Consequently the current value of ultrasonography

is the correct identification of the distal position of

the catheter. The golden rule that easily visualized

catheters may require less manipulation to be

identified ultrasonographically, should control

which catheter to use for ET. Although bladder

distension has been suggested to improve

visualization, many trials concluded that no

difference was seen after transfer with a full or an

empty bladder.

Little attention, if any, has been paid to the

unloading step and the catheter withdrawal at the

conclusion of the transfer. From my perspective,unloading of the embryos and removal of the

catheter could prove to be as critical for cycle

outcome as accurate catheter placement. The

unloading technique should be adjusted to be as

smooth as possible without the use of forceful

pressure on the syringe plunger. If the catheter tip

is put close to the fundus, vigorous pressure on the

plunger may result in the ET droplet hitting the

fundus with the subsequent spraying the droplet

back on the tip of the catheter or towards the tubal

ostia. This may affect the outcome in many ways

by reducing the pregnancy rate, increasing thepossibility of retained embryos or even ectopic

pregnancy. Unloading of the embryos, should be

monitored by US to allow each provider to

optimize his own technique. The tactile sense of

adequate plunger pressure that allow adjusted-

unloading of the embryos is a skill that will

develop with experience.

Similarly catheter withdrawal may be as critical

to the cycle outcome. Ultrasound should also guide

the catheter withdrawal as sudden withdrawal may

create a negative pressure that may either displaced

the droplet in the lower cavity or even suck it backin the catheter particularly when catheters with

outer and inner pieces are implemented. Future

research in this area should account for the

unloading step and catheter withdrawal as

confounding factors.

5. Conclusions

Although there is no adequate evidence to



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support the routine use of US during ET, we

believe that its use nowadays become a sort of

helpful risk-free practice. Moreover, it gives

reassurance and comfort to the patient seeing the

air bubble. In addition, the provider is now not

entering blindly but everything is visible and clear,

consequently there is less probability of contacting

the fundus or unloading the embryos in undesirable

locations. A very important point to consider is

that not all physicians have the same clinical skills

and experience. Consequently, it will be fairer and

comforting to use US guided ET as a routine

especially with trainees. Improvements in

ultrasound technology and catheter design with the

subsequent increase of the visibility may be

particularly useful, even if pregnancy rates are notappreciably improved.

REFERENCES

1. Kan AK, Abdalla HI, Gafar AH, Nappi L, OgunyemiBO, Thomas A, Ola-ojo OO. Embryo transfer:

ultrasound-guided versus clinical touch. Hum Reprod

1999;14:1259-1261.

2. Garcia-Velasco JA, Isaza V, Martinez-Salazar J,Landazabal A, Requena A, Remohi J, Simon C.

Transabdominal ultrasound-guided embryo transfer does

not increase pregnancy rates in oocyte recipients. FertilSteril 2002;78:534-539.

3. Matorras R, Urquijo E, Mendoza R, Corcostegui B,Exposito A, Rodriguez-Escudero FJ. Ultrasound-guided

embryo transfer improves pregnancy rates and increases

the frequency of easy transfers. Hum Reprod

2002;17:1762-1766.

4. Mirkin S, Jones EL, Mayer JF, Stadtmauer L, GibbonsWE, Oehninger S. Impact of transabdominal ultrasound

guidance on performance and outcome of transcervical

uterine embryo transfer. J Assist Reprod Genet

2003;20:318-322.

5. Sallam HN, Sadek SS. Ultrasound-guided embryotransfer: a meta-analysis of randomized controlled trials.

Fertil Steril 2003;80:1042-1046.

6. Buckett WM. A meta-analysis of ultrasound-guidedversus clinical touch embryo transfer. Fertil Steril

2003;80:1037-1041.

7. Lambers MJ, Dogan E, Kostelijk H, Lens JW, Schats R,Hompes PG. Ultrasonographic-guided embryo transfer

does not enhance pregnancy rates compared with embryo

transfer based on previous uterine length measurement.

Fertil Steril 2006;86:867-872.

8. Bedaiwy MA. Evaluation of the effect of the adoption ofultrasound guidance for embryo replacement on the

pregnancy outcome for multiple providers. Middle East

Fertil. Soc. J. 2006; 11:127-133.

9. Smith GC, Pell JP. Parachute use to prevent death andmajor trauma related to gravitational challenge:

systematic review of randomized controlled trials. BMJ

2003; 327:1459-1461.

10. Kojima K, Nomiyama M, Kumamoto T, Matsumoto Y,Iwasaka T. Transvaginal ultrasound-guided embryotransfer improves pregnancy and implantation rates after

IVF. Hum Reprod 2001;16:2578-2582.

Mohamed A. Bedaiwy, M.D.

Department of Obstetrics and Gynecology,

The Cleveland Clinic Foundation,

Cleveland, Ohio, USA.

Department of Obstetrics and Gynecology,

Assiut University Hospital, Assiut, Egypt.

Email address: [email protected]


ultrasound guidaed embryo transfer

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