Soft versus firm embryo transfer catheters for assisted reproduction: a systematic review and meta-analysis*

Ahmed M. Abou-Setta1,3, Hesham G. Al-Inany1,2, Ragaa T. Mansour1, Gamal I. Serour1 and Mohamed A. Aboulghar1,2

1 The Egyptian IVF–ET Center, 3, Street 161, Hadayek El Maadi, Cairo 11431 and 2 The Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt

3 To whom correspondence should be addressed: E-Mail: abousetta_md{at}hotmail.com; ivf{at}link.net


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
BACKGROUND: The true impact of the embryo transfer catheter choice on an IVF programme has not been fully examined. We therefore decided to systematically review the evidence provided in the literature so that we may evaluate a single variable in relation to a successful transfer, the firmness of the embryo transfer catheter. METHODS: An extensive computerized search was conducted for all relevant articles published as full text, or abstracts, and critically appraised. In addition, a hand search was undertaken to locate any further trials. RESULTS: A total of 23 randomized controlled trials (RCT) evaluating the types of embryo transfer catheters were identified. Only ten of these trials, including 4141 embryo transfers, compared soft versus firm embryo catheters. Pooling of the results demonstrated a statistically significantly increased chance of clinical pregnancy following embryo transfer using the soft (643/2109) versus firm (488/2032) catheters [P = 0.01; odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.08–1.79]. When only the truly RCT were analysed, the results were again still in favour of using the soft embryo transfer catheters [soft (432/1403) versus firm (330/1402)], but with a greater significance (P < 0.00001; OR = 1.49, 95% CI = 1.26–1.77). CONCLUSION: Using soft embryo transfer catheters for embryo transfer results in a significantly higher pregnancy rate as compared to firm catheters.

Key words: catheter/embryo transfer/ICSI/IVF/meta-analysis/randomized controlled trial


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
Embryo transfer is the final and most crucial step in IVF. About 80% of patients undergoing IVF reach the embryo transfer stage, but only a small proportion of them achieve pregnancy. The pregnancy rate after embryo transfer is dependent upon multiple factors including embryo quality, endometrial receptivity and the technique of the embryo transfer itself (Mansour and Aboulghar, 2002Go).

Recently, several surveys have shown that the embryo transfer catheter ranks high as an important, independent factor in the success of an IVF programme. A survey of Australian clinicians rated the type of catheter used as the third most important variable in embryo transfer (Kovacs, 1999Go). In addition, a postal survey in the UK found that the type of catheter used was believed to be the fourth most important variable (Salha et al., 2001Go).

The ideal embryo transfer catheter should avoid any trauma to the endocervix and/or endometrium as it finds its way into the uterine cavity. Several studies have compared different kinds of catheters for embryo transfer but most of these studies are either observational, retrospective, or are prospective but non-randomized. Even in the few prospective, randomized trials published, the majority had small sample sizes; sizes too small to reach a definite conclusion with statistical soundness. Therefore, the impact of the embryo transfer catheter choice on an IVF programme has been investigated in relatively small samples, albeit the examination of a single factor in reproductive medicine is more reliable when large groups are involved (Templeton et al., 1996Go; Ramsay, 1999Go). We therefore decided to systematically review the evidence provided in the literature so that we may evaluate a single variable in relation to a successful transfer, the firmness of the embryo transfer catheter.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
Criteria for considering studies for this review
All published, unpublished and ongoing randomized trials reporting data that compares outcomes for women undergoing embryo transfer through the cervical route following IVF, or ICSI using soft compared with firm embryo transfer catheters, were sought in all languages.

Types of outcome measures
The primary outcome measures used for this systematic review were implantation rate (IR), clinical pregnancy rate (CPR) and ongoing/take-home baby rate. The secondary outcomes were ease of transfer (catheter failure rate) and simultaneous occurrence of traumatic events (e.g. use of a tenaculum, stylette, sounding, and/or dilatation). In addition, the presence of blood, mucus and/or retained embryos on the tip of the catheter was evaluated.

Search strategy for identification of studies
A computerized search was conducted using MEDLINE (1978 to present), EMBASE (1980 to present), the Cochrane Central Register of Controlled Trials (CENTRAL) on the Cochrane Library Issue 2, 2005, and the National Research Register [a register of ongoing and recently completed research projects funded by, or of interest to, the UK’s National Health Service (NHS)] as well as entries from the Medical Research Council’s Clinical Trials Register, and details on reviews in progress collected by the NHS Centre for Reviews and Dissemination. The following Medical Subject Headings and text words were used: embryo transfer, embryo transfer technique, embryo transfer catheter, Cook, Erlangen, Frydman DT, Frydman, Gynetics, Rocket, TDT, Tom Cat, Wallace, and randomised controlled trial(s), randomized controlled trial(s) (RCTs).

Furthermore, the reference lists of all known primary studies and review articles were also examined to identify additional relevant citations. In addition, a hand search of the citation lists of relevant publications, review articles, abstracts of major scientific meetings and included studies were searched for trials. Moreover, the reviewers sought ongoing and unpublished trials by contacting experts in the field, and commercial entities.

Methods of the review
A standardized data extraction form was developed and piloted for consistency and completeness. Two reviewers (A.M.A.S. and H.G.A.I.) considered trials for inclusion, evaluated methodological quality and extracted trial data independently. Differences in interpretation were resolved by discussion and mutual agreement and refereeing by a third reviewer (R.T.M.). Data management and analysis was then conducted using the Review Manager (RevMan) 4.2 statistical software package.

Individual outcome data were included in the analysis if they met the pre-stated criteria. Where possible, data were extracted to allow an intention-to-treat analysis. If data from the trial reports were insufficient or missing, the authors contacted the investigators of individual trials for additional information, in order to perform analyses on an intention-to-treat basis.

For the meta-analysis, the number of participants experiencing the event in each group of the trial was recorded. Heterogeneity by visual inspection of the outcome tables and by using the {chi}2-test for heterogeneity with a 10% level of statistical significance was utilized.

Where statistical heterogeneity was found, the reviewers looked for an explanation. If studies with heterogeneous results were thought to be comparable, statistical synthesis of the results using a random effects model was undertaken. Furthermore, a meta-regression analysis (subgroup analyses) was undertaken to determine, if possible, the source behind the heterogeneity. In addition, the I2 test was used to attempt at quantifying any apparent inconsistency. An I2 value greater than 50% may be considered substantial hererogeneity.

In the absence of heterogeneity, results were pooled using a fixed effect model, the relative risk and risk difference [and 95% confidence intervals (CI)].

Description of studies
During the course of this review, we came across several commercially available embryo transfer catheters. They were divided into two groups: soft or firm, according to the available literature and the experience of the authors.

Soft embryo transfer catheters
The Frydman® embryo transfer catheter has a soft 23 cm long inner polyurethane catheter with an external diameter of 1.53 mm with an open end.

The Edwards–Wallace® embryo transfer catheter system set is open-ended and made of polyethylene, and has a firm outer Teflon introducer. It has an 18 or 23 cm long inner silicon catheter with an external diameter of 1.6 mm and an open end.

The Cook® Soft-Pass embryo transfer catheter system consisted of two parts fitted coaxially. The outer sheath of the catheter was 6.8 French size (FR) with an overall length of 17 cm and an inner catheter of 4.4 FR, measuring 23.5 cm. The tip of the inner sheath incorporates an echogenic stainless-steel band embedded circumferentially within a polyethylene sheath to enable its imaging at the time of transabdominal ultrasonogram.

The Cook® Soft-Trans embryo transfer catheter system set consists of a single lumen cannula with a 12.5 cm firm proximal part and a 4.0 cm soft distal part. The transfer catheter is made of an undisclosed soft polyurethane material.

The Cook® Sydney IVF® catheter system set consists of a double lumen catheter set. The guiding (outer) catheter is 19 cm long, has a polycarbonate hub, a bulb tip and the distal end is angled. The transfer (inner) catheter is 23 cm long and the tip is 2.8 French size.

The Gynetics® Delphin embryo transfer catheter is single lumen catheter set, 21 cm in length. It uses a combination of a soft, flexible intrauterine catheter and a solid cervix catheter, but is softer than Gynetics® Emtrac-A embryo transfer catheter.

Firm embryo transfer catheters
The Erlangen® embryo transfer catheter consists of an introducing metal cannula (fitted with an obturator) and an insertion catheter. The cannula has an external diameter of 2 mm, and its tip is olive-shaped with a diameter of 3 mm. The silicon movable collar is usually placed 2–3 cm from the tip. The instrument has a length of 25 cm. To facilitate handling, the proximal end of the instrument is provided with a ring to accommodate the operator’s finger. The quality of the steel used for the instrument permits the cannula to be bent to match the individual ‘angle of kink’ between the uterine corpus and the cervix.

The Tom Cat® embryo transfer catheter was initially used for draining the bladder of male cats; hence its name. It is 11.5 mm long and is made of polyethylene. The external and internal diameters of the tip are 1 mm and 0.3 mm respectively. The base is 6 mm in diameter and fits onto a 1 ml disposable syringe.

The TDT (Tight Difficult Transfer) embryo transfer catheter consists of a single lumen 18 cm long polyethylene/polyprene cannula (Frydman 4.5) and a partly polyethylene, partly metal transfer catheter. The cannula is standard equipped with a malleable metal obturator, allowing bending it into the required curve necessary for passage through the cervical canal.

The Rocket® Embryon embryo transfer catheter is 18 cm in length. The inner transfer catheter is made of polyurethane and the outer sheath is made of white polythene.

The Gynetics® Emtrac-A embryo transfer catheter is a single lumen catheter set 21 cm in length. It uses a combination of a soft, flexible intrauterine catheter and a solid cervix catheter.

A total of 23 prospective RCT evaluating the types of embryo transfer catheters were identified (10 full-text papers, 12 conference abstracts and one unpublished trial comparing different types of embryo transfer catheters). Of these studies, one was excluded because it compared a soft embryo transfer catheter to surgical placement of the embryos in the uterine cavity using a hysteroscope (Sweet et al., 1998Go). In the remaining studies, only ten trials compared soft versus firm embryo catheters including 4141 embryo transfers (Wisanto et al., 1989Go; Grunert et al., 1998Go; Amorcho et al., 1999Go; Ghazzawi et al., 1999Go; Curfs et al., 2001Go; Lavery et al., 2001Go; McDonald and Norman, 2002Go; Mortimer et al., 2002Go; Van Weering et al., 2002Go; Foutouh et al., 2003Go) (Table I). The remaining studies either compared soft versus soft transfer catheters (al-Shawaf et al., 1993Go; Mayer et al., 1999Go; Boone et al., 2001Go; Karande et al., 2002Go; Levi-Setti et al., 2002; Saldeen et al., 2003Go; Mcllveen et al., 2004Go; Taylor et al., 2005Go; Lashen, unpublished dataGo) or firm versus firm transfer catheters (Perin, 1999; Meriano et al., 2000Go; Schiewe et al., 2001).(See Figure 1a)


View this table:
[in this window]
[in a new window]
 
Table I. Review table of the prospective, randomized, controlled studies analysed, comparing soft (SC) versus firm (FC) embryo transfer catheters

 


View larger version (21K):
[in this window]
[in a new window]
 
Figure 1. Quorum flow diagram.

 

Methodological quality of included studies
The methodological quality of each trial was assessed in terms of randomization, blinding of the patients, sample size, the absence of confounders and the extent of follow-up. Each trial was judged, and given a quality rating as adequate or inadequate: A = adequate, B = unclear, C = inadequate, D = not used. Furthermore, validity scores were given to each item: A = 4, B = 3, C = 2, D = 1 and the total was tabulated (Table II). High quality trials were defined as those receiving >15 points. Moderate quality trials were defined as receiving 10–15 points. Poor quality trials were defined as receiving <10 points. Furthermore, a funnel plot assessed publication bias, quality and heterogeneity (Figures 2a,b).


View this table:
[in this window]
[in a new window]
 
Table II. Review table of the validity scores for the included studies

 



View larger version (10K):
[in this window]
[in a new window]
 
Figure 2. Funnel plots comparing soft vs firm ET catheters for all RCTs (a) and for the truly RCTs (b).

 



View larger version (37K):
[in this window]
[in a new window]
 
Figure 3. Meta-analysis of clinical pregnancy rates for all RCTs (random effects model), Truly RCTs (fixed effect model) and fresh IVF cycles only (random effects model.)

 
Randomization was considered to be proper when computer generated number tables or sealed envelopes were used. Quasi-randomization was considered to be an inadequate form of randomization. As one study used alternate randomization (Ghazzawi et al., 1999Go) and the randomization was not clear from the manuscript in five studies (Grunert et al., 1998Go; Amorcho et al., 1999Go; Lavery et al., 2001Go; Mortimer et al., 2002Go; Foutouh et al., 2003Go), only four studies described a proper method of randomization (Wisanto et al., 1989Go; Curfs et al., 2001Go; McDonald and Norman, 2002Go; Van Weering et al., 2002Go).

Furthermore, blinding was examined with regards to who was blinded in the trials. All levels were sought and categorized as follows: (i) single blind (the investigator only knew of the allocation); (ii) no blinding (both investigator and participant knew the allocated treatment); (iii) unclear. It is important to note that double blind was not sought since it would be impossible to blind the operator from knowing the type of catheter being used. In all the studies, the exact level of blindness could not be extracted; therefore they were stated as unclear.

Sample size calculations were considered to be proper when the authors of the studies pre-calculated the number needed in each arm prior to starting the trial. This prevents the occurrence of Type II errors. Only two studies (McDonald and Norman, 2002Go; van Weering et al., 2002Go) undertook sample size calculations.

As for the presence of confounders, for the purpose of this systematic review, confounders included any factors that might have helped to alter the results. These included more than one operator (as pregnancy rates are often operator dependent), testing several factors at the same time (e.g. soft versus firm catheters combined with ultrasound-guided versus clinical touch), unequal characteristics in the two groups (e.g. statistically significant differences in patient age), the transfer of fresh IVF, cryo embryos and/or donor oocytes in the same trial. Four studies (Wisanto et al., 1989Go; Grunert et al., 1998Go; Ghazzawi et al., 1999Go; McDonald and Norman, 2002Go) showed obvious presence of confounders. Furthermore, the remainder of the studies could not be considered free from confounders since either they were only published as abstracts in conference proceedings and/or the authors did not provide enough information in the text of the published manuscripts.

Finally, quality scores were assigned to each trial for completeness of follow-up. Only three studies (Grunert et al., 1998Go; Curfs et al., 2001Go; van Weering et al., 2002Go) completed follow-up until delivery; while the remaining studies were discontinued before follow-up could occur.


    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
Primary outcome measures
Implantation rate
For the implantation rate, data were only available from two studies (Grunert et al., 1998Go; Mortimer et al., 2002Go). Using the fixed effect model, there was no statistically significant difference in the chance of embryo implantation following embryo transfer using the soft (103/573) versus firm (60/360) catheters [P = 0.34; odds ratio (OR) = 1.18, 95% CI = 0.84–1.67]. However, there was statistical heterogeneity between the studies (P = 0.0003; I2 = 92.5%). Therefore, the random effects model was used for the meta-analysis, but this did not alter the results: soft (103/573) versus firm (60/360) catheters (P = 0.71; OR = 1.28, 95% CI = 0.35–4.72).

In addition, meta-regression analyses were undertaken to determine the source of the heterogeneity. Subgroup analyses were undertaken by excluding the moderate quality study (Grunert et al., 1998Go) to determine if the heterogeneity was caused by this factor. When Grunert et al. (1998)Go was removed and the results were re-analysed using the fixed effect model, this did alter the overall statistical outcome of the results in favour of the soft catheters: soft (53/170) versus firm (23/154) catheters (P = 0.001; OR = 2.51, 95% CI = 1.45–4.35).

Clinical pregnancy rate
For the clinical pregnancy rate, data were available from all ten studies. Using the fixed effect model, pooling of the results demonstrated a statistically increased chance of clinical pregnancy following embryo transfer using the soft (643/2109) versus firm (488/2032) catheters (P < 0.00001; OR = 1.39, 95% CI = 1.20–1.59). Nevertheless, there was significant statistical heterogeneity between the studies (P = 0.003; I2 = 63.4%).

In order to nullify this heterogeneity, the random effects model was utilized. Pooling of the results still demonstrated a significantly increased chance of clinical pregnancy following embryo transfer using the soft versus firm catheters (P = 0.01; OR = 1.39, 95% CI = 1.08–1.79).

In addition, meta-regression (subgroup analyses) was undertaken to determine the source of the heterogeneity. Subgroup analyses were undertaken by excluding one study at a time to determine if the heterogeneity was caused by one factor, or if multiple factors were involved. When Ghazzawi et al. (1999)Go was removed and the results were re-analysed using the fixed effect model, the heterogeneity was nullified (P = 0.15; I2 = 32.9%). However, this did not alter the overall statistical outcome of the results: soft (612/1949) versus firm (440/1872) catheters, but on the contrary it increased the statistical gap between the two groups (P < 0.00001; OR = 1.49, 95% CI = 1.49–1.73).

Furthermore, when only the fresh IVF procedure (i.e. excluding frozen replacement and donor cycles) were analysed, using the random effect model, the results were still in favour of using the soft embryo transfer catheters [soft (613/1964) versus firm (466/1882) catheters] (P = 0.02; OR = 1.38, 95% CI = 1.07–1.79).

In addition, when only the true RCT were analysed, using the fixed effect model, the results were again still in favour of using the soft embryo transfer catheters [soft (432/1403) versus firm (330/1402) catheters] (P < 0.00001; OR = 1.49, 95% CI = 1.26–1.77).

Ongoing pregnancy/take-home baby rate
For the ongoing pregnancy/take-home baby rate, data were available from three studies (Grunert et al., 1998Go; Curfs et al., 2001Go; Van Weering et al., 2002Go). Using the fixed effect model, pooling of the results demonstrated a significantly increased ongoing pregnancy/take-home baby rate following embryo transfer using the soft (290/978) versus firm (240/948) catheters (P = 0.03; OR = 1.25, 95% CI = 1.02–1.53).

Secondary outcome measures
Catheter failure
For the failure rate using the assigned catheter, data were available from five studies (Wisanto et al., 1989Go; Curfs et al., 2001Go; Lavery et al., 2001Go; McDonald and Norman, 2002Go; Van Weering et al., 2002Go). Using the random effect model, pooling of the results demonstrated a trend towards statistical significance, but this increased chance of failure following embryo transfer using the soft (100/1563) versus firm (11/1571) catheters did not reach statistical significance (P = 0.06; OR = 7.51, 95% CI = 0.94–60.11).

Traumatic events
Data pertaining to traumatic events during the embryo transfer, use of a tenaculum, stylette, sounding and/or dilatation, were recorded in three studies (Wisanto et al., 1989Go; Ghazzawi et al., 1999Go; McDonald and Norman, 2002Go). Using the random effects model, pooling of the overall results demonstrated a significantly increased chance of traumatic events during embryo transfer using the soft (229/684) versus firm (104/686) catheters (P < 0.0001; OR = 5.40, 95% CI = 1.28–222.84).

For the rate of using a tenaculum, data were available from two studies (Wisanto et al., 1989Go; McDonald and Norman, 2002Go). Using the fixed effect model, pooling of the results demonstrated a statistically increased chance of tenaculum use following embryo transfer using the soft (84/524) versus firm (62/526) catheters (P = 0.02; OR = 1.61, 95% CI = 1.07–2.43).

For the rate of using a stylette in corporation with the embryo transfer, data were available from only one study (McDonald and Norman, 2002Go), which did not use a stylette in any of the cases.

For the rate of using sounding, data were available from two studies (Ghazzawi et al., 1999Go; McDonald and Norman, 2002Go). Using the fixed effect model, pooling of the results demonstrated a significantly increased chance of need for sounding during embryo transfer using the soft (36/484) versus firm catheters (6/486) (P < 0.0001; OR = 7.45, 95% CI = 3.04–18.26).

For the rate of using dilatation, data were available from three studies (Wisanto et al., 1989Go; Ghazzawi et al., 1999Go; McDonald and Norman, 2002Go). Using the fixed effect model, pooling of the results demonstrated a significantly increased chance of need for dilatation during embryo transfer using the soft (45/684) versus firm catheters (16/686) (P = 0.0002; OR = 3.07, 95% CI = 1.70–5.54).

Catheter tip
Data pertaining to another important aspect of embryo transfer is the catheter tip. Blood, mucus, and the retention of embryos at the tip of the embryo transfer catheters were described in four studies (Wisanto et al., 1989Go; Ghazzawi et al., 1999Go; Lavery et al., 2001Go; McDonald and Norman, 2002Go). Using the random effects model, pooling of the overall results demonstrated a significantly increased chance of these events during embryo transfer using the soft (163/1328) versus firm (55/1320) catheters (P < 0.02; OR = 5.63, 95% CI = 1.32–24.02).

Blood on the tip of the catheter was described in two studies (Wisanto et al., 1989Go; McDonald and Norman, 2002Go). Using the fixed effect model, there was no significant difference between the two groups: soft (42/524) versus firm (39/526) (P = 0.37; OR = 1.10, 95% CI = 0.67–1.79).

Mucus on the tip of the catheter was described in one study (Ghazzawi et al., 1989). There was a significantly increased chance of finding mucus on tip of the catheter in the soft catheter group (65/160) when compared with the firm catheter group (0/160) (P = 0.0002).

Retained embryos were described in three studies (Ghazzawi et al., 1999Go; Lavery et al., 2001Go; McDonald and Norman, 2002Go). Using the random effects model, there was a trend towards increased likelihood of retained embryos using the soft catheters (56/644) versus firm catheters (16/634), but this did not reach statistical significance (P = 0.05; OR = 4.52, 95% CI = 1.01–20.28).


    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
Although most patients who undergo assisted procreation, via IVF or ICSI, reach the embryo transfer stage and have embryos of good quality available for transfer, embryo implantation remains the rate-limiting step in the success of this form of therapy. The main factors that affect embryo implantation are uterine receptivity, embryo quality, and efficiency of the embryo transfer procedure. The aim must be to transfer the embryos with a high degree of reliability atraumatically.

There have been many publications over the years discussing ways of improving embryo transfer and hopefully pregnancy rates. Multiple factors may affect the success of uterine embryo transfer including the experience of the physician (Lu, 1999Go), the use of ultrasound guidance (Buckett, 2003; Sallam and Sadeek, 2003Go), the ease of the procedure (Lesny et al., 1998Go), the presence or absence of blood on the catheter (Goudas et al., 1998Go) and bacterial contamination of the catheter (Egbase et al., 1996Go). In addition, other factors concerning embryo transfer that might affect the chance for an ongoing pregnancy have been identified, such as the use of cervical introducers or obturators (Ghazzawi et al., 1999Go), the value of resting after transfer (Woolcott and Stanger, 1997Go), the position of embryo insertion in the uterus (Yovich et al., 1985Go; Waterstone et al., 1991Go), flushing of the cervical canal to remove mucus (Sallam et al., 2000Go), microbiological factors in terms of the local flora (Ralph et al., 1999Go) and retention of embryos in the catheter (Friedler et al., 1993Go; Moore et al., 2000Go). Since it would be difficult to compare several factors at the same time, we decided to concentrate on one factor, the firmness of the embryo transfer catheter, as a possible cause of limiting the success of the embryo transfer.

One crucial factor that has not gained enough attention and scrutiny as a deciding factor is catheter technology. There is no conclusive evidence for the preferred use of any particular catheter and previous randomized trials have been too small to show significant differences in pregnancy rates. Moreover, some authors have concluded that the success rate of embryo transfers is not even influenced by the choice of the embryo transfer catheter used (Diedrich et al., 1989Go). Therefore the catheter choice has been mainly left to personal choice, availability and implied cost-effectiveness.

Several embryo transfer catheters are commercially available. All are mainly composed of non-toxic plastics and/or metal, but vary in length, calibre, location of the distal port (end- or side-loading), and degree of stiffness and malleability. These catheters can be subdivided by the material they are made of (i.e. metal, hard or soft plastics) and whether they are equipped with, or without, an introducing cannula that facilitates the transfer procedure.

In this systematic review, soft embryo transfer catheters overall performed better compared with the firm embryo transfer catheters. Even though the implantation rate seemed to be questionable in favour of the soft catheters, there is definitely a strong statistical trend for clinical pregnancies using the soft catheters. This was apparent in the clinical pregnancy and ongoing pregnancy/take-home baby rate.

One theory why the softer catheters produce better results is built on decreasing the trauma to the endometrium. The softer the materials used, the lesser the chance for damage to the endometrium and the lesser the chance for uterine contractions. The soft transfer catheters follow the natural curvature of the uterine cavity better than the firmer catheters, possibly reducing the risk of burrowing into the posterior endometrium in the anteflexed uterus, or stimulating uterine junctional zone contractions. This is supported by the ultrasound-detected endometrial changes following intrauterine insemination, which differ between firm and soft catheters (Lavie et al., 1997Go). The Tom Cat catheter was shown to cause significantly more trauma to the endometrium than did the Edwards–Wallace catheter. In addition, a retrospective analysis of 518 embryo transfers, comparing five catheters [firm (Tefcat, Tom Cat, Norfolk) and soft (Frydman, Wallace)] found that a soft catheter was associated with higher pregnancy rates than a firm catheter (Wood et al., 2000Go). The results of this meta-analysis confirm that this increased pregnancy rate is both statistically and clinically significant.

In contrast, the soft catheters were also associated with a higher degree of failure to negotiate the cervix and therefore the simultaneous occurrence of traumatic events (use of tenaculum, stylette, sounding and/or dilatation). In addition, they had a higher rate of blood, mucus and retained embryos at the tip of the embryo transfer catheter, but overall these events did not seem to alter the pregnancy rates.

Passing soft catheters through the cervical canal is often difficult and even sometimes impossible. In a series of 876 embryo transfer procedures by Wood et al. (1985)Go, 1.3% were impossible, 3.2% were very difficult (requiring manipulation for >5 min or cervical dilatation) and 5.6% were difficult (requiring manipulation) to perform. In another study by Mansour et al. (1990)Go, soft catheters resulted in the highest rate (37.6%) of difficult embryo transfer with the consequences of lowering the pregnancy rate. Furthermore, difficult transfers have been associated with lower pregnancy rates (Mansour et al., 1990Go; Lesny et al., 1998Go). Our review supports the theory that softer catheters are associated with a higher incidence of difficult transfers, but not negatively affecting the pregnancy rates.

Since difficult transfers have been associated with a poorer outcome than easy transfer, it would be useful to directly examine the uterine cavity for any lesions post-transfer. Unfortunately, this would not be possible without ultimately affecting the pregnancy rate. Therefore indirect measures of the degree of difficulty are utilized. These include patient discomfort during the procedure, the need for use of a tenaculum, stylette, sounding and/or cervical dilatation, and the presence of blood on the catheter post-transfer.

Different approaches have been described in cases of difficult embryo transfers with varying success rates (Mansour et al., 1990Go; Kato et al., 1993Go; Groutz et al., 1997Go; Tur-Kaspa et al., 1998Go). A commonly used initial approach is to negotiate the cervix using the outer sheath of the catheter, with its inner noodle withdrawn (Glass et al., 2000). Once the uterine cavity is entered, the inner noodle is used to deposit the embryos, taking care to avoid the fundus.

Even though this technique works efficiently in certain situations, in others it is not sufficient. Therefore more invasive and potentially traumatic events are sometimes undertaken by clinicians to overcome the problematic cervix. These include the use of a tenaculum, stylette, sounding and/or cervical dilatation. Overall these events have been associated with increased uterine junctional zone contractions and a decreased pregnancy rate (Visser et al., 1993Go; Groutz et al., 1997Go; Lesny et al., 1998Go, 1999Go). Alternatively, the cervical route may be bypassed and the embryos may be transferred transmyometrially into the uterine cavity using the ‘Towako method’ (Kato et al., 1993Go).

Another tell-tale sign of a difficult transfer is the post-transfer presence of blood on the transfer catheter. Amongst clinicians, the absence of blood on the catheter or cannula is ranked high as an important factor towards success (Kovacs, 1999Go). This opinion is supported by literature reports in which the presence of blood on the transfer catheter has been associated with lower pregnancy rates (Visser et al., 1993Go; Goudas et al., 1998Go). In addition, Perin et al. (1999)found that contamination of the catheter with blood and mucus accounted for significantly lower implantation and clinical pregnancy rates. In our review, even though these events were present more frequently with the softer catheters, it did not seem to drastically alter the outcome.

Finally, the incidence of retained embryos was shown in this review to be higher with the softer embryo catheters. The role of retained embryos in decreasing the pregnancy rate is controversial with some studies claiming a negative effect (Visser et al., 1993Go) and other claiming no such effect (Nabi et al., 1997; Goudas et al., 1998Go). Again, we could not confirm that the increased incidence of retained embryos with the soft catheters had any great influence on the overall outcome.

In conclusion, the results of this study clearly indicate that the type of embryo transfer catheter contributes significantly to the success rate of an IVF programme. Soft catheters rather than firm catheters are associated with better pregnancy rate, even though a soft catheter is also associated with more traumatic events. More adequately powered, high quality RCT are needed to support the development of an ideal soft catheter that finds its way to the cavity with minimal failure rate.


    Acknowledgements
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
The authors would like to thank all the corresponding authors that were contacted for more information and provided us with assistance. Special thanks to Dr Janelle McDonald, Dr Robert Norman and Dr Raja Karaki, whose direct assistance has helped to increase the accuracy of this systematic review by providing us with missing information.


    Notes
 
* Part of this manuscript was presented orally during the European Society of Human Reproduction and Endocrinology’s 2005 Annual Meeting (Copenhagen, Denmark). Back


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
al-Shawaf T, Dave R, Harper J, Linehan D, Riley P and Craft I (1993) Transfer of embryos into the uterus: how much do technical factors affect pregnancy rates? J Assist Reprod Genet 10,31–36.[CrossRef][ISI][Medline]

Amorcho B, Gomez E, Pontes L, Campos I and Landeras J (1999) Does the selection of catheter for embryo transfer affect the success rate of an ART unit? [abstract] 15th Annual Meeting of the ESHRE (Tours, France), 1999. Hum Reprod 14(Suppl 1)205.

Boone WR, Johnson JE, Blackhurst DM and Crane MM 4th (2001) Cook versus Edwards–Wallace: are there differences in flexible catheters? J Assist Reprod Genet 18,15–17.[CrossRef][ISI][Medline]

Buckett WM (2003) A meta-analysis of ultrasound-guided versus clinical touch embryo transfer. Fertil Steril 80, 1037–1041.

Curfs MHJM, Cleine JH, van Kamp AA, Kruse-Blankestijn ME, Hondelink MN and Leerentveld RA (2001) Comparison of the Wallace versus TDT embryo-transfer catheter: a prospective, randomized study. Third Biennial Alpha Conference, September 8–11, 2001, New York, New York, USA. Reprod Biomed Online : 3(Suppl 1).

Diedrich K, Van der ven H, Al-Hasani S and Krebs D (1989) Establishment of pregnancy related to embryo transfer techniques after in-vitro fertilization. Hum Reprod 4(Suppl 1),111–114.

Egbase PE, al-Sharhan M, al-Othman S, al-Mutawa M, Udo EE and Grudzinskas JG (1996) Incidence of microbial growth from the tip of the embryo transfer catheter after embryo transfer in relation to clinical pregnancy rate following in-vitro fertilization and embryo transfer. Hum Reprod 11,1687–1689.[Abstract]

Foutouh IA, Youssef M, Tolba M, Rushdi M, Nakieb A and Meguid WA (2003) Does embryo transfer catheter type affect pregnancy rate? Middle East Fertil Soc J 8,154–158.

Friedler S, Lewin A and Schenker JG (1993) Methodology of human embryo transfer following assisted reproduction. J Assist Reprod Genet 10,393–404.[CrossRef][Medline]

Ghazzawi IM, Al-Hasani S, Karaki R and Souso S (1999) Transfer technique and catheter choice influence the incidence of transcervical embryo expulsion and the outcome of IVF. Hum Reprod 14,677–682.[Abstract/Free Full Text]

Glass KB, Green CA, Fluker MR, Schoolcraft WB, McNamee PI, Meldrum DR (2000) Multicenter randomized controlled trial of cervical irrigation at the time of embryo transfer. (abstract no. O-085) Fertil Steril 74 (Suppl 1) S31.

Goudas VT, Hammitt DG and Damario MA (1998) Blood on the embryo transfer catheter is associated with decreased rates of embryo implantation and clinical pregnancy with the use of in vitro fertilization–embryo transfer. Fertil Steril 70,878–882.[CrossRef][ISI][Medline]

Groutz A, Lessing JB, Wolf Y, Yovel I, Azem F and Amit A (1997) Cervical dilation during ovum pick-up in patients with cervical stenosis: effect on pregnancy outcome in an in vitro fertilization–embryo transfer program. Fertil Steril 67,909–911.[CrossRef][ISI][Medline]

Grunert GM, Dunn RC, Valdes CT, Wun CC and Wun WSA (1998) Comparison of Wallace, Frydman DT and Cook embryo transfer catheter for IVF: a prospective randomised study [abstract]. Annual Meeting of the American Society of Reproductive Medicine, 1998. Fertil Steril 70, S120.

Karande V, Hazlett D, Vietzke M and Gleicher N (2002) A prospective randomized comparison of the Wallace catheter and the Cook Echo-Tip catheter for ultrasound-guided embryo transfer. Fertil Steril 77,826–830.[CrossRef][ISI][Medline]

Kato O, Takatsuka R and Asch R (1993) Transvaginal–transmyometrial embryo transfer: the Towako method; experience of 104 cases. Fertil Steril 59,51–53.[ISI][Medline]

Kovacs GT (1999) What factors are important for successful embryo transfer after in-vitro fertilization? Hum Reprod 14,590–592.[Free Full Text]

Lashen H (unpublished data) A prospective randomised trial comparing two embryo transfer catheters. National Research Register (NRR): http://www.nrr.nhs.uk/ViewDocument.asp?ID=N0059115928

Lavery S, Ravhon A, Skull J, Ellenbogen A, Taylor J, Dawson K, Trew G, Margara R and Winston R (2001) A prospective randomized controlled trial of Wallace and Rocket embryo transfer catheters in an IVF–embryo transfer programme [abstract]. Hum Reprod 16(Suppl 1),124.

Lavie O, Margalioth EJ, Geva-Eldar T and Ben-Chetrit A (1997) Ultrasonographic endometrial changes after intrauterine insemination: a comparison of two catheters. Fertil Steril 68,731–734[CrossRef][ISI][Medline]

Lesny P, Killick SR, Tetlow RL, Robinson J and Maguiness SD (1998) Embryo transfer: can we learn anything new from the observation of junctional zone contractions? Hum Reprod 13,1540–1546.[Abstract]

Lesny P, Killick SR, Tetlow RL, Robinson J and Maguiness SD (1999) Embryo transfer and uterine junctional zone contractions. Hum Reprod Update 5,87–88.[Free Full Text]

Levi-Setti PE, Albani E, Baggiani AM, Zannoni E, Colombo G, Liprandi V (2002) Prospective randomized study comparing two soft catheters for embryo transfer. Fertil Steril 78;3(Suppl 1)S234.

Lu MC (1999) Impact of ‘non-physician factors’ on the ‘physician factor’ of in vitro fertilization success: is it the broth, the cooks, or the statistics? Fertil Steril 71,998–1000.[CrossRef][ISI][Medline]

Mansour R and Aboulghar M (2002) Optimizing the embryo transfer technique. Hum Reprod 17,1149–1153.[Abstract/Free Full Text]

Mansour R, Aboulghar M and Serour G (1990) Dummy embryo transfer: a technique that minimizes the problems of embryo transfer and improves the pregnancy rate in human in vitro fertilization. Fertil Steril 54,678–681.[ISI][Medline]

Mayer JF, Nechiri F, Jones EL, Weedon VM, Kalin HL, Lanzendorf SE, Oehinger SC, Toner JP and Muasher SJ (1999) Prospective randomized analysis of the impact of two different transfer catheters on clinical pregnancy rates [abstract]. ASRM/CFAS Conjoint Annual Meeting September 25–30, 1999 (Toronto, Canada). Fertil Steril (Suppl 1), S144–145.[CrossRef]

McDonald JA and Norman RJ (2002) A randomized controlled trial of a soft double lumen embryo transfer catheter versus a firm single lumen catheter: significant improvements in pregnancy rates. Hum Reprod 17,1502–1506.[Abstract/Free Full Text]

Mcllveen M, Lok D, Pritchard J and Lashen H (2004) A randomised controlled trial comparing two embryo transfer catheters. Hum Reprod 19,127S.

Meriano J, Weissman A, Greenblatt EM, Ward S and Casper RF (2000) The choice of embryo transfer catheter affects embryo implantation after IVF. Fertil Steril 74,678–682.[CrossRef][ISI][Medline]

Moore DE, Soules MR, Klein NA, Fujimoto VY, Agnew KJ and Eschenbach DA (2000) Bacteria in the transfer catheter tip influence the live-birth rate after in vitro fertilization. Fertil Steril 74,1118–1124.[CrossRef][ISI][Medline]

Mortimer S, Fluker M and Yuzpe A (2002) Effect of embryo transfer catheter on implantation rates [abstract]. 58th Annual Meeting of the American Society for Reproductive Medicine. Fertil Steril 78(3), S17–18.

Nabi A, Awonuga A, Birch H, Barlow S, Stewart B (1997) Multiple attempts at embryo transfer: does this affect in-vitro fertilization treatment outcome? Hum Reprod 12,1188–1190.

Perin PM (1999) The influence of two different transfer catheters on the pregnancy rate in a human in vitro fertilization program. Reprod Clim 14,81–88.

Ralph SG, Rutherford AJ and Wilson JD (1999) Influence of bacterial vaginosis on conception and miscarriage in the first trimester: cohort study. Br Med J 319,220–223.[Abstract/Free Full Text]

Ramsay S (1999) Experts give practical advice in reproductive medicine. Lancet 354,51.[CrossRef][Medline]

Saldeen P, Bergh T, Sundstrom P and Holte J (2003) A prospective randomized controlled trial comparing two embryo transfer catheters in an ART programme [abstract]. 19th Annual Meeting of the European Society of Human Reproduction and Embryology. Hum Reprod 18(Suppl 1),130–131.[CrossRef]

Salha OH, Lamb VK and Balen AH (2001) A postal survey of embryo transfer practice in the UK. Hum Reprod 16,686–690.[Abstract/Free Full Text]

Sallam HN and Sadek SS (2003) Ultrasound-guided embryo transfer: a meta-analysis of randomized controlled trials. Fertil Steril 80,1042–1046.[CrossRef][ISI][Medline]

Sallam HN, Farrag F, Ezzeldin A, Agameya A, Sallam AN (2000) Vigorous flushing of the cervical canal prior to embryo transfer, a prospective randomised study. Fertil Steril 74;3(Suppl 1)S203.

Schiewe M (2001) IVF-ICSI pregnancy outcomes in a randomized embryo transfer catheter trail comparing the cook soft-pass catheter to the Edward–Wallace catheter [abstract] (2001) 51st Annual Meeting of the American Society of Reproductive Medicine, Fertil Steril 76;3(Suppl 1),181.[CrossRef]

Sweet CR, Hamidi J, El Mansari El, Guttieri T and Harrington T (1998) Hysteroscopic vs. catheter embryo transfer: a randomized prospective pilot study. American Society Reproductive Medicine (San Francisco, USA). Fertil Steril 70,(Suppl 1)S331.

Taylor TH, Colturato LF, Jones AE, Wright G, Elsner CW, Kort HI and Nagy ZP (2005) Prospective comparison of three soft ET catheters. Hum Reprod 20(Suppl 1), i130.

Templeton A, Morris JK and Parslow W (1996) Factors that affect outcome of in-vitro fertilisation treatment. Lancet 348,1402–1406.[CrossRef][ISI][Medline]

Tur-Kaspa I, Yuval Y, Bider D, Levron J, Shulman A and Dor J (1998) Difficult or repeated sequential embryo transfers do not adversely affect in-vitro fertilization pregnancy rates or outcome. Hum Reprod 13,2452–2455.[Abstract]

van Weering HG, Schats R, McDonnell J, Vink JM, Vermeiden JP and Hompes PG (2002) The impact of the embryo transfer catheter on the pregnancy rate in IVF. Hum Reprod 17,666–670.[Abstract/Free Full Text]

Visser DS, Fourie FL and Kruger HF (1993) Multiple attempts at embryo transfer: effect on pregnancy outcome in an in vitro fertilization and embryo transfer program. J Assist Reprod Genet 10,37–43.[CrossRef][ISI][Medline]

Waterstone J, Curson R and Parsons J (1991) Embryo transfer to low uterine cavity. Lancet 337,1413.[ISI][Medline]

Wisanto A, Janssens R, Deschacht J, Camus M, Devroey P and Van Steirteghem AC (1989) Performance of different embryo transfer catheters in a human in vitro fertilization program. Fertil Steril 52,79–84.[ISI][Medline]

Wood C, McMaster R, Rennie G, Trounson A and Leeton J (1985) Factors influencing pregnancy rates following in vitro fertilization and embryo transfer. Fertil Steril 43,245–250.[ISI][Medline]

Wood EG, Batzer FR, Go KJ, Gutmann JN and Corson SL (2000) Ultrasound-guided soft catheter embryo transfers will improve pregnancy rates in in-vitro fertilization. Hum Reprod 15,107–112.[Abstract/Free Full Text]

Woolcott R and Stanger J (1997) Potentially important variables identified by transvaginal ultrasound-guided embryo transfer. Hum Reprod 12,963–966.[CrossRef][ISI][Medline]

Yovich JL, Turner SR and Murphy AJ (1985) Embryo transfer technique as a cause of ectopic pregnancies in in vitro fertilization. Fertil Steril 44,318–321.[ISI][Medline]

Submitted on April 21, 2005; resubmitted on June 12, 2005; accepted on June 16, 2005.





This Article
Abstract
Full Text (PDF )
All Versions of this Article:
20/11/3114    most recent
dei198v2
dei198v1
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Search for citing articles in:
ISI Web of Science (2)
Request Permissions
Google Scholar
Articles by Abou-Setta, A. M.
Articles by Aboulghar, M. A.
PubMed
PubMed Citation
Articles by Abou-Setta, A. M.
Articles by Aboulghar, M. A.