In this study we aimed to assess endometrial evolution in order to ascertain a plausible predictive non-invasive diagnostic tool for clinicians to better understand endometrium changes.
The pregnancy potential of good quality embryos is still not high on ART cycles, even with the progress in the programs of ovarian stimulation, ART technique and embryo development and culture. Implantation is still strongly reliable on the cross talk between a healthy good quality embryo and the receptive endometrium.
Although several parameters have been used to assess the pregnancy rate in ART cycles, there is still some controversy about its efficacy, and underlying mechanisms in endometrial receptivity (15-18). Vaginal 3D ultrasound is a non-invasive and an inexpensive tool at clinician’s disposal. (19) The process of endometrial transformation from proliferative phase to secretory phase under the steroids hormonal influence, called endometrial decidualization is a set goal for optimal implantation. The cyclic changes of endometrium are regulated by ovarian hormones and its receptors, and endometrial luteal phase development may alter in ART cycles due to supraphysiological hormone levels.
Single analysis of endometrial pattern at trigger day has been the most used, with contradictory findings.
Recent studies (Silva Martins, R. et al.) have proven that perhaps serial evaluations provide better understanding rather than a single scoop at a pre-determined phase of the process. It has been proven that in terms of angiogenesis that there is a certain pattern of evolution. This relates to what one should expect from a transforming living tissue and its natural adaptations on the complex binding process of implantation.
The main purpose of this study was to further evaluate potential ultrasonographic markers that might be evaluated in the continuous changes that endometrium goes through during an ART cycle. The possibility to use non-invasive techniques to determine endometrial receptivity would allow better clinical judgment. This way on the clinical point of view, the decision to transfer a fresh embryo on that same ART cycle or postpone it for a deferred transfer with better endometrial conditions is possible. This non-invasive tool to predict endometrial receptivity will improve clinical setting and allow better understanding of endometrial receptivity. This may be the way to optimize and achieve greater results in ART cycles.
In our study endometrial morphology proven not to be useful and no significant difference was found between the two groups. Also 2-D endometrial thickness showed no difference at early stages of ovarian controlled stimulation, but significant difference could be seen after day 8 of stimulation. These findings are compatible to the ones provided by the literature. The main reason for such may be the fact that subjective tools produce conflicting results and therefore are not able to provide an accurate diagnostic tool for endometrial receptivity assessment.
Endometrial volume and adjusted endometrial volume proven to be more effective with differences shown since early stages of ovarian controlled stimulation. Both groups were similar at baseline but as soon as controlled ovarian stimulation started, the differences between the ones with a positive outcome and the negative group were clearly met.
We have also been able to show differences between the two groups in terms of endometrial and adjusted endometrial volume in early stages of endometrial development under the influence of controlled ovarian stimulation. Higher volumes were seen in the positive controls, but the changes were more evident in early stages (especially between day 6 and day 8 of ovarian controlled stimulation). This is also corroborated by the fact that growth rate was statistically higher on the positive group, but the higher difference was met in early stages of endometrial development (between day 6 and day 8). The supraphysiological environment produced by the controlled ovarian stimulation may have leading role in such. Our study showed that serial continuous endometrial volume was significantly higher on the positive group, whereas studies from Kupesic et al., and Wu et al., (20,21) have conflicting results in the assessment of endometrial receptivity. The difference can possibly be explained by the fact of serial continuous evaluations better reflect endometrial changes, rather than predetermined single scoop analysis.
The use of a cut off ≥ 5mL in endometrial volume in prediction of endometrial receptivity had a good sensitivity and low specificity and may be used as a good test to exclude success. The fact that we can have a tool that indicates a non-optimal endometrium aids in the decision process of postponing embryo transfer for a more suitable and receptive endometrium.
The possibility of real time non-invasive continuous assessment of the endometrium further induces clinicians to better medical decisions. The current study demonstrated that it is possible to evaluate endometrial morphologic parameters, serial endometrial volume and adjusted serial endometrial volume in the coronal plane in accordance with published method by Mercer et al. (22)
All findings may prove to be a useful management tool for clinicians in order to establish a diagnostic tool for better decision making in selective embryo transfers.
Nevertheless, one must always be cautious that artefacts during 3D analysis may occur due to 2D imaging process, patient motion during rendering of images and artefacts due to operator choice in the selection of which part of the volume to display. (23)
We could not refrain to uphold expectation of these promising results as they show a serial of values, demonstrating a certain pattern of evolution on a transforming living tissue and its natural adaptations to a complex and yet unknown process. The authors would like to raise awareness to a controversial topic, with a different uptake on the question of non-invasive methods to assess endometrial receptivity. We have successfully been able to obtain limited data concerning a preferential pathway on endometrial volumetry. However larger studies should be carried out to further sustain our findings.