Fig. 5.1
Measuring the utero-cervical angle by transabdominal ultrasonography (a) no angle, (b) small angle (<30°), (c) moderate angle (30°–60°), (d) large angle (>60°) (Used with permission from Sallam et al. [44])
Soft Catheters Versus Rigid Catheters
It has been suggested that soft ET catheters should be associated with a better outcome when compared to firm catheters, and two meta-analyses of RCTs confirmed that soft catheters were indeed associated with a higher clinical pregnancy rate (OR = 1.34, 95 % CI = 1.17–1.53) [47, 48]. However, when soft and firm catheters were compared in patients undergoing ultrasound-guided ET, a meta-analysis found no difference in clinical and ongoing pregnancy rates between them [49]. This confirms the fact that a prior knowledge of the uterine configuration (including the utero-cervical angle) may help the clinician in conducting a smoother ET, even if he is using a firm catheter.
Presence of Air in the Transfer Catheter
The presence of two small air bubbles surrounding the embryo-containing droplet in the ET catheter does not seem to affect the outcome of IVF or ICSI. Moreno et al. [50] conducted an RCT on 102 patients and found no difference in the clinical pregnancy rate between the presence and the absence of these air bubbles [50].
Site of Embryo Deposition
The best site for embryo deposition has been a matter of debate. In 2002, Coroleu et al. conducted an RCT and found that depositing the embryo 1.5–2 cm away from the uterine fundus was associated with a significantly higher clinical pregnancy rate (31.3 %, 33.3 %) compared to depositing it 1 cm below the fundus (20.6 %) [51]. These findings were later confirmed by Pope et al., who performed a regression analysis study and showed that for every additional millimeter embryos are deposited away from the fundus, the odds of clinical pregnancy increased by 11 % [52].
Time Between Loading and Discharging the Embryos
The time between loading the embryos in the ET catheter and discharging them into the uterine cavity is critical as the embryos may be affected by being outside the CO2 incubator. In an observational study, Matorras et al. [53] found that the clinical pregnancy rate started decreasing significantly when the loading-to-discharging time lapse exceeded 120 s [53].
Waiting 30 s After Embryo Deposition
Many clinicians prefer to wait for 30 s after embryo deposition before withdrawing the ET catheter from the uterine cavity. This practice was studied by Martinez et al. [54], who found no significant difference in clinical pregnancy rate when the catheter was withdrawn immediately after embryo deposition or after 30 s. They concluded that either waiting was not necessary or that waiting a longer time may improve the outcome, but this latter point has not so far been clarified [54].
The Use of a Fibrin Sealant
Different substances have been added to the embryo-containing droplet in order to increase its capacity to adhere to the endometrium with various claims of success. Bar-Hava et al. [55] used a fibrin sealant for this purpose and found that this practice increased the clinical pregnancy rate significantly [55]. However, an RCT did not confirm these findings [56]. Similarly, Valojerdi et al. [57] conducted a quazi-randomized study using embryo glue but could not find any significant difference in the clinical pregnancy rate [57]. However, a Cochrane review of RCTs found that this practice was associated with a significantly higher clinical pregnancy rate (OR = 1.41; 95 % CI = 1.22–1.63) but the live birth rate remained unchanged [58].
Bed Rest After ET
Various studies have been conducted to investigate whether bed rest after ET would improve the outcome of IVF and ICSI, with most of them showing no advantage of keeping the patient in bed after ET [59–61]. A Cochrane systematic review on the subject concluded that bed rest after ET had no effect on the clinical pregnancy (OR = 1.33; 95 % CI = 0.77–1.67) or live birth (OR = 1.00; 95 % CI = 0.54–1.85) rates [62].
Routine Use of Antibiotics
Various studies have shown that infection in the cervical mucus has a detrimental effect on the outcome of IVF and ICSI [63–65]. Infection can be confirmed by culturing a swab taken from the cervical mucus or from the tip of the catheter after ET. We have conducted a meta-analysis of these studies and found that cervical infection was indeed associated with a lower clinical pregnancy rate (OR = 0.42; 95 % CI = 0.29–0.60) [66].
Administering antibiotics to women undergoing ET was also a matter of controversy. Egbase et al. [67] cultured the tip of the catheter after ET and prescribed prophylactic antibiotics to patients with positive cultures. They found that the clinical pregnancy rate increased significantly from 18.7 % to 41.3 % (P < 0.01) after the use of antibiotics [67]. However, administering prophylactic antibiotics to all patients undergoing IVF or ICSI did not affect the outcome of ET. Peikrishvili et al. [68] conducted an RCT and prescribed amoxicillin and clavulanic acid to half of their patients, while the other half served as controls. They found no significant difference in the implantation rate between both groups [68]. Similar conclusions were reported by Brook et al. [69], who conducted a similar RCT in 2006 [69].
Experience of the Clinician
The experience of the clinician seems to play an important role in determining the outcome of ET. Hearns-Stokes [70] analyzed the results of two clinicians performing ET in the same unit with embryos provided by the same embryologist and found a significant difference in the clinical pregnancy rate between both clinicians (17 % versus 54.7 %; P < 0.05). They concluded that training of clinicians is essential before allowing them to perform ET on their own [70]. Furthermore, well-trained nurses have been found to perform as good if not better than clinicians in two studies, and many units are now allowing their trained nurses to perform ET [71, 72]. Papageorgiou et al. [73] found that the learning curve requires at least 50 ETs. These should be done under supervision before the clinician or nurse is allowed to perform ET on his own [73].
Conclusions
Despite its apparent simplicity, ET is affected by many variables. RCTs have shown that ultrasound guidance, mid-fundal deposition of the embryos, performing ET with a full bladder and using a soft catheter rather than a rigid one (if no ultrasound guidance is used) are associated with significantly higher clinical pregnancy rates. They have also shown that difficult transfers and cervical infection decrease the clinical pregnancy rate significantly. On the contrary, RCTs have shown that bed rest after ET, waiting 30 s after ET, sexual intercourse after ET, the presence of air in the ET catheter, the use of a fibrin sealant, performing the ET under the effect of acupuncture, performing ET in the lithotomy rather than the knee-chest position and the routine use of antibiotics do not affect the outcome of the procedure. Finally, performing a dummy ET, removing the cervical mucus before ET, flushing the cervical canal before ET and avoiding the use of a tenaculum require further evaluation.
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