Embryo transfer (ET) is an apparently simple procedure, but still not fully understood. Several variables play a role in the success of the embryo implantation: quality of embryos, grade of endometrial receptivity and not the least, the procedure of transfer. In fact, it is estimated that a poor technique is responsible for up to 30% of the in vitro fertilization (IVF) failure.
The aim of this study is to identify the pre- and intra-operative parameters to predict the degree of difficulty of ET and to establish the relationship between difficult ET and pregnancy rate (PR) in patients undergoing ART.
In this prospective study will be recruit 80 patients, candidates for ET following IVF/ intracytoplasmic sperm injection (ICSI). ET will perform with the use of ultrasound guidance pre and during the entire procedure, in order to evaluate different parameters: the anatomical features, the thickness of the endometrium, the grade of bladder distension, the need for additional manoeuvres, and the classification of the procedure in easy or difficult according by the surgeon assessment. A pregnancy test will be performed 15 days after the transfer, in order to verify the status of pregnancy of the patients.
The results of this study may contribute to determinate the pre- and intra- operative parameters correlated to difficult embryo transfer and to evaluate their impact on reproductive outcomes in IVF.
Embryo transfer is the last critical step in an IVF cycle.
Constant advances of ART in safer, more efficient stimulation schemes and better laboratory techniques have been done but there have been no major changes in the ET technique in recent years.
Despite the apparent simplicity of the ET difficult transfers are frequent and its impact on the success of the entire cycle is unclear.
Different studies have evaluated the likely of a significantly decrease pregnancies rate (PR) following a complicate ET procedure but the evidences are still contradictory and inconsistent.
In 1998 Tur-Kaspa et al. first conducted a study focused on this field; they divided patients in 4 groups base on technical difficulties experienced during embryo transfer and compared the pregnancy rate, resulting no statistically different in each groups. This study first described the principal difficult to perform an ET but many later papers have highlight that their conclusions are incorrected due to confounding factors.
On the contrary, in the following years many evidences have demonstrated that a difficult ET is a negative prognostic factor in terms of pregnancy probability. Similar results are then present in several other studies. Englert et al. have reported that the PR were 33% in "easy ET" compared to 10.5% in "difficult ET". Mansour et al. have shown that difficult ET is related to a reduction of PR and also of Implantation Rate. Tomàs et al. have quantified in 1.7 times higher PR in case of easy or intermediate transfer compared to a difficult transfer.
In 2012 Phillips et al. performed a systematic review and meta-analysis to examine whether a difficult embryo transfer or the presence of blood on the transfer catheter affects assisted reproduction outcomes. They confirmed that embryo transfers subjectively considered to be difficult or those that require additional manoeuvres and/or instrumentation have a negative effect on PR. Moreover, their evidence suggested that the presence of blood at ET does not affect the chance of achieving a clinical pregnancy. The results of the review are limited by the different definitions used to define a difficult ET and by the low quality of the evidences.
In 2017 Kava-Braverman et al. have conducted a large retrospective study to establish the relationship between the degree of difficulty of ET and PR. A total of 7,714 ETs were analyzed. The PR was significantly higher in the cases of easy ET compared with difficult ET (38.2% vs. 27.1%). Each instrumentation needed to successfully deposit the embryos in the fundus involves a progressive reduction in the PR. They claimed the possible reasons for low PR in difficult ET as endometrial lesions and the induction of uterine contractions caused by the intervention. The limitations of this study are its retrospective design and the combined analysis of the different ARTs with fresh and frozen embryo transfer. They cannot rule out the possibility that the different hormonal preparations used for each type of ET could modulate the effect of the procedure.
Recently, in 2021, Inal et al. have investigated whether embryo transfer affects pregnancy rates including a total of 2,257 patients who underwent IVF-ICSI treatment between 2012 and 2017. Subjects were categorized according to the embryo transfer technique that was required: group 1 (n=657) underwent easy transfer with a soft catheter; group 2 (n=548) received external guidance transfers; and group 3 (n=52) experienced difficult transfers with a stylet.
In contrast with the previous studies, their data suggest that PRs were comparable between the groups, then embryo transfer has no impact on pregnancy rates in patients who undergo IVF-ICSI treatment. The potential weakness of the study is that the cumulative CPR was not evaluated because no frozen ETs were included.
The main objective of the ET is to deposit the embryo inside the uterine cavity. It is crucial that this be performed atraumatically and in a correct position to achieve proper implantation. Different hypothesis have been formulated to
explain how a difficult ET may reduce PR, the main ones being endometrial lesion and the induction of uterine contractions that may compromise correct embryo implantation.
Considering the importance of a good ET technique as the final step in ART, every effort should be made to optimize it.
The innovation of this study lies in the intent to standardize the use of an accurate pre and intraoperative evalutation of anatomical characteristics of the patient, with the aim of identify and classify "Easy ET" and "Difficul ET".
For the first time, we will analyze single anatomical and procedural parameters separately, in order to understand the single impact on the reproductive outcomes. Moreover, we will enroll only fresh ET and subsequently we will reduce confounding factors. The results of our study may be useful regarding how to regard ET as difficult and to optimize ART outcomes.