The results of our study showed that HyLiFoSy-PD had high diagnostic accuracy for tubal patency assessment, with reference to LDT. The results reported by our study are comparable to those reported in a recent systematic review and meta-analysis that summarized the results of some HyFoSy studies. In this analysis, the included studies reported sensitivity between 89 and 100%, specificity (39–100%), PPV (47–100%), NPV (80–100%), positive LR 11.5 (95% CI, 1.5–87.5), negative LR 0.006 (95% CI, 0.0003–0.12), and overall accuracy (60–100%) .
The accuracy of HyFoSy, using ExEm gel foam, and its comparability to HSG and LDT in tubal patency assessment were reported before by multiple studies [3, 5, 6, 8, 9, 15,16,17, 19,20,21,22]. However, ExEm gel is not available in Egypt and other developing countries. It is also relatively expensive to lidocaine in countries where it is available. On the other hand, the high availability, low cost, and proven safety of lidocaine gel use intrauterine  inspired us to test the technique described by Ludwin et al. in 2017, which describes the use of lidocaine-made gel foam as a contrast medium for HyFoSy procedures . The equipment needed for this procedure were very few, affordable, and easily available. These included 2 syringes, a pediatric Foley’s catheter, saline, and xylocaine gel.
We did not add three-dimensional (3D) ultrasound to our examination as the assessment of tubal patency using 3D-HyLiFoSy-PD versus 2D-HyLiFoSy-PD by the same sonographer carries the risk of bias. However, we believe that standardized automated pelvic scanning and offline reconstruction of images using 3D-HiLiFoSy, if the facilities and experience are available, can help make the procedure quicker, less painful, more reproducible, and less operator-dependent [1, 5, 8, 16, 20, 27].
Doppler imaging can increase the diagnostic accuracy of HyFoSy , it also facilitates the identification of tubal occlusion . In our experience, PD was found to be helpful in the confirmation of the direction of foam flow as well as the acceleration during the injection. However, we believe that greyscale 2D-HyFoSy, alone, can be of good accuracy as well if performed by an experienced sonographer [1, 8].
A possible limitation to our study was using VRS for pain assessment instead of the more accurate visual analog scale (VAS) and numeric rating scale (NRS) . However, we believe that VRS was practical, easier to understand, and more convenient to use with our patients than VAS or NRS. Moreover, we assessed pain in our study at one point of time, while VAS and NRS are more powerful in the detection of change in pain . This may not be the case in developed countries, where the facilities (paper, pen, assistant) and patients’ literacy help make VAS and NRS more applicable to use for pain assessment.
Using VRS, 91 (79%) patients in our study reported mild pain, 24 (21%) reported moderate pain, and seven patients experienced severe pain, which correspond to scores 1–3, 4–6, and 7–10 of the VAS and NRS, respectively . This lies in line with the pain score results reported by HyFoSy studies that used VAS and NRS to assess pain [10, 16, 21, 28,29,30]. This suggests that HyLiFoSy-PD is a well-tolerated procedure, like HyFoSy, that can be carried out without pre-procedural analgesia [1, 5, 6].
The pre-procedural use of NSAIDs, intrauterine infusion of local anesthetic (lidocaine), procedure duration (11 min), and 2 ml filling of balloon catheter were sources of potential bias and might have affected the pain results in our study. However, the use of pre- procedural analgesia was described in multiple HyFoSy studies, with some of them also assessed (pain) as an outcome [1, 10, 15, 16, 24]. Furthermore, in spite of the intrauterine use of lidocaine, all patients experienced some degree of pain. This confirms the findings of most previous studies done on the pre-procedural use of lidocaine, which reported that it was not effective in reducing pain [1, 18, 23].
Since the procedure duration was only reported in two previous HyFoSy studies done by the same author with medians of 5 and 5.5 min, we are not sure that a longer procedure duration (median: 11 min) in our study could have raised the pain scores, as the author did not note how the procedure duration was calculated [21, 30]. The definition and calculation of the procedure duration may be considered in future HyFoSy studies to enable comparability.
In attempts to reduce pain, balloon-less intrauterine catheters were used in multiple HyFoSy studies using ExEm gel foam [5, 8, 9, 18,19,20,21, 30], while other studies used balloon catheters and inflated them with 0.5–1.5 ml of saline [10, 15, 16, 24, 28, 29]. However, an earlier study found no difference in pain scores between different size balloon catheters and balloon-less others . Therefore, we rule out the possibility that our 2-ml saline filling of the balloon catheter could have raised the pain scores.
In our study, seven patients experienced severe pain, and the procedure was canceled. Marked obesity was a criterion in four of them (BMI: 40, 35, 35, 34), retroverted uterus in two, and pulled-up cervix with a history of myomectomy in three. In our experience, difficult access to the cervix was associated with severe pain. This was related to obesity, retroverted uterus, and adhesions due to previous surgeries. On the other hand, it was reassuring to find that no other side effects or complications were encountered in any of the patients during and after the procedure. Also, the echogenicity resulting from lidocaine-made gel foam was visible on ultrasound for the whole HyLiFoSy-PD procedure, with an estimated average of 11 min in all patients.
Another potential source of bias in our study was the sample consisting of unselected infertile patients with a low prevalence of tubal occlusion. However, this was suitable for estimating the diagnostic accuracy of a HyLiFoSy-PD as a screening tool for tubal patency. Finally, doing HyLiFoSy-PD before LDT might have affected LDT results, as proximal tubal ostium spasm [1, 5] or tubal unlocking might had happened during HyLiFoSy-PD. For this, we carried out HyLiFoSy-PD 1 week before the scheduled LDT. Also, successive tubal testing with the index and reference tests was done in other HyFoSy studies [1, 6, 15, 16, 20]. Finally, tubal spasm and false tubal occlusion results can occur with LDT alone as well [1, 5, 16].
To the best of our knowledge, this is the first study to investigate the diagnostic accuracy of HiLiFoSy-PD in tubal patency assessment. Blinding of sonographers, endoscopists, and statisticians was a point of strength to our study. Given the high sensitivity (98.1%) of HyLiFoSy-PD measured in our study, we suggest that it can be a good screening tool for tubal patency that can be carried out as an office procedure using conventional 2D TV-US system, minimal equipment, and some ultrasound training on the technique. Negative results (occluded tubes), however, may warrant further tubal testing with LDT or other tubal tests, especially in the absence of risk factors or a history highly suspicious of tubal occlusion .
In conclusion, HyLiFoSy-PD using lidocaine-made gel foam was found to be an accurate, safe, and feasible tool for tubal patency assessment. It can be carried out as an office procedure by an experienced sonographer using a 2D TV-US system. Our opinion is that it can be a possible substitute for HyFoSy that uses ExEm gel foam whenever the gel is not available or is relatively expensive compared to lidocaine. Further research should be carried out to validate our results.