Embryo Transfer (ET): The Techniques
The goal of embryo transfer (ET) is their placement in the uterus with minimal trauma to the endometrium and embryos.
The essential features of ET in human females remain unchanged since the first description by Robert Edwards nearly 30 years ago. Traditionally, scant attention has been focused on the technique of ET, which is often viewed as an unimportant variable in the success of an IVF cycle, and clinicians are often reluctant to change their habits or methods regarding this procedure.
In 1982, Leeton and his group described the technique for ET. They compared the success rate while using "end-opening" and "side-opening" ET catheters. The use of end-opening catheters produces a slight advantage in pregnancy rate.
Many factors have been proposed to explain the disparity between embryonic development and pregnancy rates. Much of the inefficiency of embryo implantation may be applicable to the ET technique. Uterine contractions, expulsion of embryos, blood or mucus on the catheter tip, bacterial contamination of the catheter, and retained embryos have all been associated with problematic and unsuccessful ETs.
The goal of transcervical ET is to deliver embryos in a gentle, nontraumatic fashion, to the uterine fundus, a location where implantation is maximized. The avoidance of blood or mucus on the catheter tip, retained or expelled embryos, and the generation of uterine contractions is of utmost importance. The use of a precycle trial transfer, as well as ultrasound guidance and cervical lavage, and “soft” catheters appears to increase the chance of a successful outcome. Careful attention to the numerous details of the ET technique appears to be as important as the efforts of the embryologist in the laboratory.
Type of Catheter
Several types of catheters are available: stiff versus soft materials, end- and side-openings, the presence of an outer sheath, malleability, and quality of the materials and finish. Whereas stiff catheters and the use of a rigid outer sheath make catheter placement easier, they may result in more bleeding, trauma, mucus plugging, and stimulation of uterine contractions. The use of soft catheters that facilitated the tip in following the contour of the cervical and uterine access, and minimized trauma to the endometrium (Wallace catheter), was first described by Edwards and colleagues in 1984.
The change from the stiff catheter (Tomcat) to the soft catheter (Wallace catheter) has been associated with an improvement in pregnancy and implantation rates, as well as fewer catheters exhibiting blood, mucus, or retained embryos.
Loading the Catheter
Considerable variation in the volume and constitution of the medium loaded in the catheter has been noted. Some clinicians prefer using fluid alone, or mixture of air and fluid in the catheter during transfer. A large volume (60 µL) of transfer media and a large air interface may result in expulsion of embryos into the cervix, on the speculum, or adhere to the exterior of the catheter.
Removal of the air column can minimize such complications. Several studies have reported an increase in pregnancy and implantation rates after reducing the amount of air and the ??total transfer volume. Others reported high pregnancy rates using a continuous fluid column of 30 .µL in a Wallace catheter attached to a 1 cc airtight syringe. The embryos are loaded preferentially toward the tip of the embryo column closest to the catheter opening
Performing a trial ET prior to the actual procedure
Performing a trial (mock or simulated) ET before the actual transfer has been suggested in an effort to increase pregnancy and implantation rates. Several studies have been published on this topic. However, only one of these was a randomized, controlled trial (RCT) in which the authors reported that the pregnancy and implantation rates were significantly higher in the simulated-transfer group compared to the conventional-transfer group.
Removing the cervical mucus prior to ET
Consequently, removal of the cervical mucus prior to ET has been claimed to improve pregnancy and implantation rates, but to date no randomized trials have been published on the routine aspiration of the mucus prior to ET.
Flushing the cervical canal with culture medium prior to ET
It has also been claimed that vigorous flushing of the cervical canal with culture medium prior to ET can improve implantation in assisted reproduction. However, in a RCT performed with and without flushing, no statistically significant difference was noted in pregnancy or implantation rates.
The catheter may be inserted in one of two techniques: Blind insertion by “clinical touch” or with the aid of ultrasound guidance. It has been shown that blind catheter insertion resulted in the inadvertent placement of the catheter touching the fundus.
Use of ultrasound for ET has many potential advantages, such as:
Facilitates the placement of soft catheters
• Avoids contact with the fundus
• Confirms that the catheter is beyond the internal os in cases of an elongated cervical canal
• Facilitates catheter guidance along the contour of the endometrial cavity
• Enables assessment of the ovaries and detection of the presence of excessive peritoneal fluid volume to confirm or rule out the presence of severe ovarian hyperstimulation syndrome (OHSS) that may preclude ET
• Rules out fluid in the endometrial cavity
• A full bladder, required to perform trans abdominal ultrasound guidance, is, in itself helpful in straightening the cervical uterine access and improving pregnancy rates.
In 1985 Strickler and his group were the first to report the use of ultrasound guidance for ET. It was found that ultrasound-guided ET were easier and were associated with less catheter distortion. Over the years several reports clearly showed an increase in pregnancy rate when insertion of the catheter was guided by ultrasound.
Ultrasound image with ET under full bladder (Taken from the "Advanced Fertility Center" in Chicago at: http://www.advancedfertility.com/embryotransfer.htm
Problematic access into the cervix: Is this of importance?
In the past, it was suggested that the ease or difficulty of the transfer did not really affect outcome. Much evidence exists to the contrary. Difficult ETs had significantly lower pregnancy and implantation rates compared to easy transfers.
Occasionally, cervical stenosis or acute angulations between the cervix and the uterus limits uterine access and makes ET difficult. Utilized cervical dilatation 2 days prior to ET resulted in very low pregnancy rates. It has been suggested that a short interval between dilatation and transfer was apparently not long enough for the endometrium to recover from any trauma, inflammation, or bacterial contamination induced by the dilatation. However, it was found that performing cervical dilatation prior to initiation of the treatment cycle resulted in easier transfers and improved pregnancy rates.
When cervical stenosis or angulation persist at the time of transfer, thus prohibiting the placement of a soft catheter, a malleable stylet can be used to place the outer sheath of a Wallace catheter beyond the internal os. The stylet is then removed and the inner clear catheter inserted. Using this technique, pregnancy and implantation rates, equivalent to “easy” transfers with the Wallace catheter, were obtained.
The above photographs were taken from the P-M Group website at: http://www.pmgrouponline.com/wallace/wallace.htm
Alternatively, the “Towako Procedure” can be performed, in which embryos are replaced by transmyometrially, thereby circumventing any possible problems with the cervix. This was first described in 2001 in a patient with congenital cervical atresia. This procedure has not gained much popularity.
Holding the cervix with a tenaculum was found to stimulate uterine contractions. Elevation in oxytocin level was reported when the tenaculum was applied to the cervix during ET, affecting implantation of the transferred embryos. With a difficult ET, strong random uterine contractions and fundocervical uterine contractions were detected. Uterine contractions progressively decrease as one moves/enters further into the luteal phase, following the increase in progesterone concentrations, and this may be a contributing factor in the success of day 5 blastocyst stage ETs.
Location of the embryos in the uterus
Implantation rate was found to be significantly higher when the embryos were deposited 2 cm instead of 1 cm below the fundus. This was also found to be associated with a lower incidence of ectopic pregnancies.
Is rest needed after the transfer?
In a nonrandomized study, it was reported that in females who had no bed rest after ET the clinical pregnancy rate was significantly higher compared with a control group. This finding was
confirmed in a randomized controlled study published in 1997 by Botta and Grudzinskas who found no statistically significant differences in clinical pregnancy rate between patients who had a 24-hour period of bed rest following ET compared to those who had bed rest for 20 minutes only. This study was supported by the observation published in 1998 by Woolcott and Stanger who examined the effect of standing, immediately after transfer, on the movement of the embryo fluid column/air interface. No movement was detected in 94%, 4 cm in only 2% of cases, respectively.
Sexual intercourse should not be avoided before or after the procedure. On the contrary, it was shown that implantation rates were significantly increased for patients who had sexual intercourse at approximately the time of ET.