1 Suite 14, John James Medical Centre, 175 Strickland Crescent, Deakin, ACT 2600 and 2 The Reproductive Medicine Unit, The Queen Elizabeth Hospital and Wakefield Clinic, Department of Obstetrics and Gynaecology, University of Adelaide, Australia
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Abstract |
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Key words: catheter/embryo transfer/IVF/pregnancy rates/randomized controlled trial
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Introduction |
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At the time of planning the trial our pregnancy rates in fresh IVF cycles were relatively disappointing in spite of excellent embryology services and very experienced clinical staff. We hypothesized that a higher pregnancy rate could be achieved by changing the embryo transfer protocol. Prior to the trial we had routinely used the Tom Cat catheter for embryo transfer. Our aim was to compare pregnancy rates in IVF with the single lumen Tom Cat catheter (TCC) and the double lumen Cook catheter (CC).
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Materials and methods |
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The catheters
The Tom Cat catheter (Kendell Health Care, Hampshire, MA, USA) 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 Tom Cat catheters used were all from one batch and were subject to mouse embryo testing by an external observer (Dr Patrick Quinn, SAGE BioPharma, CA, USA). A bend was placed on the end of the catheter whilst maintaining a sterile technique.
The Cook Catheter (K-JETS-7019-SIVF; Cook IVF, Eight Miles Plains, Queensland, Australia) is a double lumen catheter set. The guiding (outer) catheter is 19 cm long, has a polcarbonate 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 base of the transfer catheter fits onto a 1.0 ml plastic syringe. All catheters used in the trial were from the same batch, and the batches are mouse embryo tested during manufacture.
The embryo transfer
The catheters were prepared by the embryologist prior to transfer. Embryo transfer procedures were carried out in a treatment room 4872 h after oocyte retrieval or at corresponding times following ovulation in frozen cycles. A maximum of three embryos was transferred. The clinician performing the transfer was not aware of the catheter allocated prior to the procedure. It was not possible to be certain that the patient was blind to the catheter used as it may have been visualized by the woman at embryo transfer. We did however avoid discussion regarding the catheter used during and following the transfer. All women were placed in the lithotomy position and no sedation was required. A bivalve speculum was inserted to visualize the cervix. The cervix was cleaned with a cotton wool swab soaked in culture media. The embryos were loaded by the embryologist into the allocated catheter in 10 µl of culture media. The loaded CC set was handed to the clinician with the tip of the transfer catheter situated inside the guiding catheter. The guiding catheter was passed through the cervical canal until the bulb tip was located just beyond the internal os of the cervix. The transfer catheter was then advanced 2 cm and the embryos were deposited. The loaded TCC was introduced to 60 mm, aiming to deposit the embryos just short of the uterine fundus. The respective catheter was kept in the uterus for 3060 s and was then slowly withdrawn. The CC set was withdrawn without moving the transfer catheter back inside the guiding catheter. The tip of the TCC and the tip of the Cook transfer catheter were immediately inspected by the embryologist for the presence of a retained embryo. It was thought to be unnecessary to inspect the Cook guiding catheter for a retained embryo.
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Results |
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Analysis of individual clinicians' results found that embryo transfer was, to some extent, operator dependent (Table II). There was substantial variability in pregnancy rates with the CC. However, experience was not a factor, with inexperienced clinicians achieving results as good or better than experienced clinicians. In contrast, pregnancy rates in all clinicians were remarkably similar when the TCC was used (Table II
). Eight clinicians participated in the study but one (I) ceased working for the clinic shortly after the trial commenced. The other clinicians had worked in IVF for variable times at the commencement of the trial (1 month to 20 years) and all participated fully for the duration of the trial. They included two registrars in subspecialty training, one nurse practitioner and four specialists in reproductive medicine. The four clinicians (B, C, D and G) with the highest pregnancy rates using the CC and with the greatest differences between the two catheters included both registrars and two very senior clinicians with many years experience in IVF. The results for all clinicians were as good or better with the CC compared with the TCC (Table II
).
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Discussion |
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There are a number of plausible theories to explain why the CC is associated with higher pregnancy rates. The tip of the TCC is harder than the tip of the CC and may cause more trauma to the endometrium. The soft transfer catheter of the CC may follow the natural curvature of the uterine cavity better than the TCC, possibly reducing the risk of burrowing into the posterior endometrium in the anteflexed uterus. This is supported by the ultrasound detected endometrial changes following intrauterine insemination which differ between hard and soft catheters (Lavie et al., 1997). In this study the TCC was associated with loss of the endometrial three layer pattern after 50% of treatments with the hard TCC and 12.5% with the soft Wallace catheter. The guiding catheter of the CC is firmer than the TCC and may protect the embryos from physical trauma during the passage through the cervical canal. The tip of the transfer catheter of the CC is protected within the guiding catheter when contact is made with the cervix, potentially reducing contamination of the embryos by cervical flora.
Embryo transfer may be operator dependent to some degree. We were encouraged to find that inexperienced IVF clinicians were able to achieve excellent pregnancy rates with the CC. This suggests that the CC is user friendly with a short learning curve. All but one clinician in our study had not used the CC regularly prior to the study period. A recent audit on training in embryo transfer found that trainees using the Wallace catheter achieved equivalent results to experienced staff by the time they had done 50 transfers (Papageorgiou et al., 2001). In our study clinicians B, C and G achieved improved pregnancy rates with only a small amount of experience with the CC (Table II
). The results varied substantially according to clinician (Table II
) but the numbers treated by each clinician are not sufficient to give an indication as to whether this was due to other factors. It is possible that expectations played a role in this difference. Unfortunately, it is impossible to blind clinicians performing the transfer and difficult to blind patients to the catheter used.
There have been many publications over the years discussing ways of improving embryo transfer and hopefully pregnancy rates. Most data have been descriptive and collected retrospectively. Factors that have been studied include the use of soft versus hard catheters (Meriano et al., 2000; Wood et al., 2000
), ultrasound guidance for embryo transfer (Letterie et al., 1999
; Wood et al., 2000
), use of cervical introducers or obturators (Ghazzawi et al., 1999
), the value of resting after transfer (Woolcott and Stanger, 1998
), the position of embryo insertion in the uterus (Yovich et al., 1985
; Waterstone et al., 1991
), flushing of the cervical canal to remove mucus (Sallam et al., 2000
) and microbiological factors in terms of the local flora (Ralph et al., 1999
) and contamination of the catheter tip. The live birth rate after IVF is influenced by the presence of bacteria in the catheter tip (Moore et al., 2000
). Lactobacillus and S. viridans were associated with increased and decreased live births respectively.
Previous studies of catheters have been predominantly observational studies with only five small randomized controlled trials, none of which have directly compared the CC with the TCC (Wisanto et al., 1989; al-Shawaf et al., 1993
; Ghazzawi et al., 1999
; Meriano et al., 2000
; Boone et al., 2001
). These have been often contradictory and have not led to a consensus on the preferred catheter. Other than two studies comparing the Frydman and Wallace catheters, there are no trials that compare the same catheters. This precludes meta analysis. A retrospective analysis of 518 embryo transfer, comparing five catheters [hard (Tefcat, Tom Cat, Norfolk) and soft (Frydman, Wallace)] found that a soft catheter was associated with higher pregnancy rates than a hard catheter (Wood et al., 2000
). Wood also found that ultrasound guidance, when good visualization was obtained, led to better pregnancy results than those cycles where there was poor visualization. There was no significant difference in pregnancy rates when the degree of difficulty of embryo transfer was considered in both catheter groups.
Combined data from three small prospective randomized trials totalling 429 embryo transfer with an average of 3.2 embryos transferred per embryo transfer compared the Cook soft-pass catheter with the EdwardsWallace catheter and found no significant difference in pregnancy rates (39% versus 43%) (Boone et al., 2001) (Table III
).
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On the whole (including this study) soft catheters have been associated with better outcomes. Data suggesting that hard catheters are better than soft catheters is limited to two questionable studies. A small (n = 66) prospective randomized trial compared the TCC with the TDT catheter and concluded that the TCC achieved higher pregnancy rates than the TDT catheter (47 versus 15%) (Meriano et al., 2000). The sample size was, however, very small and results for both groups were extreme, suggesting that no sample size calculation had been performed and that the study was prematurely terminated. Also, the authors mention that the TDT catheters were from more that one batch and do not state that embryo toxicity testing was carried out. A retrospective comparison of the TCC and the Frydman catheter evaluated 193 embryo transfer and found that the TCC performed significantly better than the Frydman (29 versus 16%) (Gonen et al., 1991
).
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Conclusions |
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Acknowledgements |
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Notes |
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References |
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Submitted on September 20, 2001; accepted on January 16, 2002.