Embryo Transfer Catheters: Softer is Easier

Claudio Ruhlmann; Diego C Gnocchi; Antonio R Cattaneo; Lucas G. Molina; Luciano Ruiz Rivadeneira; Lautaro Tessari; Alejandro G. Martínez

JBRA Assist. Reprod. 2015;19 (4):204-209
ORIGINAL ARTICLE
doi: 10.5935/1518-0557.20150040

Embryo Transfer Catheters: Softer is Easier

Claudio Ruhlmann¹, Diego C Gnocchi¹, Antonio R Cattaneo¹, Lucas G. Molina¹, Luciano Ruiz Rivadeneira¹, Lautaro Tessari¹, Alejandro G. Martínez¹

¹Fertilidad San Isidro – San Isidro, Buenos Aires, Argentina

Received July 27, 2015
Accepted September 23, 2015

Corresponding author:
Alejandro Gustavo Martínez
Fertilidad San Isidro
San Isidro, Buenos Aires, Argentina
E-mail: agmartinez@fibertel.com.ar

CONFLICT OF INTERESTS
No conflict of interest have been declared.

ABSTRACT
Objective: This study aimed to compare the use of semi-rigid and flexible catheters in terms of pregnancy rate and level of difficulty of the embryo transfer (ET) procedure.
Methods: Seven hundred and thirty-nine consecutive follicular aspirations for IVF or ICSI performed in our private fertility clinic within a 30-month period were randomly divided into two groups. Patients were allocated to either of the groups at the time of follicular retrieval with the aid of a random number generator according to the catheter used in ET: Group 1 (n = 370) – Frydman Classic Catheter 4.5 catheters; and Group 2 (n = 369) – Frydman Ultrasoft 4.5 catheters. Only patients offered ET in the randomized cycle were included (Group 1 = 363 and Group 2 = 340). Patients did not change groups after catheter allocation.Statistical analysis was carried out using an unpaired t-test or a chi square test as appropriate. Differences with P<0.05 were considered.
Results: A statistically significant difference in favor of the use of the Ultrasoft catheter was evident for parameters use of a tenaculum (19.8% vs. 5.9%) or a hysterometer (5.0% vs. 1.2%), presence of blood during post-ET inspection of the catheter (9.9% vs. 3.8%), and implantation rate (13.0% vs. 16.4%). Clinical pregnancy and delivery rates were comparable in both groups.
Conclusions: Our results suggest that a softer catheter may help with difficult ETs. Softer catheters, as also reported by other authors, resulted in better implantation rates.

Keywords: Embryo transfer, transfer catheter, IVF/ICSI, pregnancy rate

INTRODUCTION
The success of assisted reproductive technology (ART) procedures depends on three stages: controlled ovarian hyperstimulation, in vitro embryonic development, and embryo transfer (ET). The importance of this last step is frequently overlooked. ET is considered an easy and simple procedure, which has not been considerably modified in the last two decades. The impact of different factors related to ET on the implantation rate has been prospectively evaluated in small samples or retrospective studies (Abou-Setta et al., 2005; Mains & Voorhis et al., 2010).
The following factors related to ET may affect the likelihood of achieving an ongoing pregnancy.
• Operator experience (Groeneveld et al., 2012; Kably Ambe et al., 2011; Karande et al., 1999; Lu et al., 1999; Hearns-Stokes et al., 2000; Yao et al., 2009).
• Bladder filling (Lorusso et al., 2005; Pope et al., 2004).
• Transfer depth (Coroleu et al., 2002; de Camargo Martins et al., 2004; Friedman et al., 2011; Pope et al., 2004).
• Performing the procedure under ultrasound control (Abou-Setta et al., 2007; Buckett et al., 2003; Coroleu et al., 2000; Kan et al., 1999; Matorras et al., 2002; Sroga et al., 2010; Pope et al., 2004; Wood et al., 2000).
• Degree of difficulty of the procedure (Lesny et al., 1998; Sallam & Sadek, 2003; Spitzer et al., 2012).
• Presence of blood or mucus in the catheter during post transfer inspection (Goudas et al., 1998; Mains & Van Voorhis, 2010; Moragianni et al., 2010; Nabi et al., 1997; Schoolcraft et al., 2001; Vasiliki et al., 2010; Van Weering et al., 2002).
• Bacterial contamination (Egbase et al., 1999; Moore et al., 2000; Sallam & Sadek, 2003).
• Type of catheter used (Abou-Setta et al., 2005; Gonen et al., 1991; Meriano et al., 2000; Saldeen et al., 2008; Sallam & Sadek, 2003; Van Weering et al., 2002).
Some authors have reported better pregnancy rates when using more flexible catheters, despite an association with increased ET procedure difficulty (Abou-Setta et al., 2005; Kably Ambe et al., 2011; Mansour et al., 1990; Saldeen et al., 2008; Spitzer et al., 2012; Wood et al., 1985). We have been using semi-rigid Frydman® Classic 4.5 catheters (CCD Laboratoire, Paris, France) for over ten years in our ET procedures. However, we have recently incorporated the more flexible Frydman® Ultrasoft 4.5 catheters into our ART program.
This prospective trial aimed to compare the success rates and difficulty of ET procedures derived from the use of semi-rigid and more flexible catheters.

MATERIALS AND METHODS
Patients and procedures
Seven hundred and thirty-nine consecutive follicular aspirations for IVF or ICSI followed by ET performed in our private fertility clinic within a 30-month period were included. Patients were randomized using a random number generator and were divided at the time of follicular aspiration into two groups according to the catheter chosen for ET.
• Group 1 (n = 370): Frydman® Classic Catheter 4.5 (CCD Laboratoire, Paris, France, catalog # 1306045).
• Group 2 (n = 369): Frydman® Ultrasoft Catheter 4.5 (CCD Laboratoire, Paris, France, catalog # 1324201).
Patients did not change groups after random allocation.
Only patients offered ET in the cycle in which they were randomized were included. Exclusion criteria: lack of retrieved mature oocytes; failed complete fertilization or cleavage; no fresh sperm available; endometrium unfit for ET; extreme difficulty or impossibility when performing the mock ET; or cycle cancellation to prevent ovarian hyperstimulation syndrome (OHSS). Patients were not excluded for age, low ovarian response, or high levels of baseline FSH. A mock transfer was performed under ultrasound guidance on the day of follicular aspiration to evaluate the distance between the external cervical os and the uterine fundus and the degree of difficulty in accessing the uterine cavity. In the study group, ultrasound guidance was used during ET only in the cases in which increased difficulty had been identified during the mock transfer.
To perform the ET, patients were placed in dorsal lithotomy position and a sterile speculum was placed to expose the uterine cervix. The cervix was sanitized with sterile gauze soaked with PBS (Irvine, USA), and the external cervical os cleaned the same way.
The embryos were placed into the distal end of the catheter in the laboratory. The catheter was then delivered to the operator to perform the ET. After passing through the cervix, the end of the catheter was placed 1.2 to 1.5 cm from the previously measured fundus of the uterus, where the embryos were gently discharged. The catheter was then gently removed and returned to the laboratory to verify whether embryos were retained in it.
Twelve days after transfer the serum level of HCG beta subunit was measured; the test was repeated 48 hours later. Four weeks after ET, transvaginal ultrasound examination was performed to confirm the presence of gestational sac(s) in the patients with positive pregnancy tests.

Measurements
The following parameters were used to estimate the degree of difficulty of the ET procedure: the utilization of a tenaculum or a hysterometer; the need for ultrasound guidance due to difficulties during the mock transfer; and the presence of blood and/or embryo retention in the catheter after the transfer attempt.
ET efficacy was estimated based on implantation rate, clinical pregnancy rate, and delivery rate.

Statistical analysis
The historical ET clinical pregnancy rate was approximately 25%. This value was used as a reference in the calculation of the sample size. Three hundred and forty were required in each group to detect a difference of 10% in the clinical pregnancy rate with a power of 80% and a significance level of 5%.
ET procedures were divided into consecutive quartiles to assess the impact of a possible learning curve, particularly with the newly incorporated catheter, and to allow a statistical comparison of their relative degree of difficulty and efficiency parameters across the study.
For statistical analysis an unpaired t-test or a chi square test was applied as appropriate. Statistical significance was attributed to differences with a P<0.05.

Ethics and approval
This randomized prospective comparative study was carried out in accordance with the guidelines of our Institutional Review Board. The study was not awarded grants or financial sponsorship of any kind.

RESULTS
Seven hundred and nine of the 739 randomized follicular aspirations were included in the study, 363 in Group 1 (semi-rigid catheter) and 340 in Group 2 (flexible catheter). The remaining 36 were ruled out for meeting any of the exclusion criteria (Table 1).
A comparison of the demographic and clinical data of the patients revealed that the subjects in Group 2 had undergone more ET procedures and taken GnRH antagonists more often (Table 2).
Every patient allocated to each specific group completed the embryo transfer procedure with the assigned catheter.
A tenaculum or hysterometer was used more often in individuals in Group 1, and more individuals in this group had blood in their catheters after ET and required ultrasound guidance during the procedure. More cases of embryo retention in the catheter after attempted ET procedures were seen in Group 2 (Table 3).
In terms of efficacy parameters, a higher implantation rate was seen in Group 2. Clinical pregnancy and delivery rates were comparable in both groups (Table 4).
The parameters concerning degree of difficulty remained constant for the semi-rigid catheter across the study, whereas for the newly incorporated flexible catheter there was a decrease in the use of a tenaculum (Tables 5 and 6).

Table 1. Randomization allocation and exclusions

Table 2. Patient demographic and clinical data

Table 3. ET difficulty parameters for semi-rigid and flexible catheters

Table 4. Efficacy parameters for semi-rigid and flexible catheters

Table 5. Degree of transfer difficulty and efficiency parameters over time for the semi-rigid catheter

Table 6. Randomization allocation and exclusions

DISCUSSION
Differently from previous publications, our results showed that ET could be performed with less difficulty when more flexible catheters were used. This finding challenges the widespread belief that the use of a rigid catheter is superior when dealing with a difficult cervical canal. The ability to adapt to curvatures or obstacles in the canal and the isthmic-cervical angle is probably a more valuable feature than the rigidity of the catheter.
Occasionally, difficulty with ET requires the use of a tenaculum to modify the isthmic-cervical angle or a hysterometer in the event of a stenosis that could not be overcome by the catheter. These procedures can cause bleeding and uterine contractions, both of which contribute to a decrease in ART success rate (Fanchin et al., 1998). The difficulties that can be encountered in ET are generally caused by cervical stenosis or a more pronounced anteversion/retroversion or anteflexion/retroflexion of the uterus (Garzo, 2006). These are the cases in which employing a rigid catheter requires the introduction of a tenaculum or a hysterometer to adapt the uterine angle to the shape of the catheter. These difficulties were resolved with the use of a flexible catheter, possibly due to the ability of the device to adapt to the uterine anatomy without the need for the aforementioned maneuvers.
Unlike previous studies in which flexible catheters were difficult or impossible to use (Madani et al., 2010), none of the ET procedures in our study group required the replacement of the catheter. This is probably due to the fact that mock transfers were performed beforehand in all cases with the catheters that would be used in the ET procedure.
In the present study, the level of difficulty of the ET procedure was significantly lower when the more flexible catheter was used despite the minimal experience surgeons had with it. The comparative advantage of the flexible catheter grew as operators became more used to it, as seen in the comparison between first and last quartile results (Table 6).
This finding stresses the importance of the learning curve when an element recently incorporated to the system is compared to one traditionally used, especially when the study sample is small. It has been proven that operator experience may have an impact in pregnancy rates after ET (Desparoir et al., 2010).
The presence of blood after ET has been associated with an increase in embryo retention (Goudas et al., 1998; Ressler, 2013). This complication requires a new transfer attempt. In our study, the incidence of retained embryos was significantly higher with the flexible catheter, although there were no increases in the blood contamination in post-ET catheter inspection.
Embryo retention is possibly affected by the characteristics of the materials from which catheters are manufactured or the need to adjust the syringe used in each catheter design. These factors had no impact on success rates.
The implantation rate is the most reliable indicator of efficiency in the ART process.
A significant increase in implantation rates was achieved with the use of the more flexible catheter. Clinical pregnancy and delivery rates were comparable in both groups.
Greater difficulty during ET has been associated with lower pregnancy and implantation rates (Tomas et al., 2002; Listijono, 2013; Ressler, 2013).
Our results suggest that the selection of the type of catheter used, together with adequate training when a new element is incorporated into the clinical practice, might have a significant effect on the degree of difficulty and efficiency of the ART process.
Based on the present study, the flexible catheter is now the device of choice in our clinic.