Comparison of the Diagnostic Accuracy of Hysterosalpingo-lidocaine-foam Sonography Versus Hysterosalpingography in Tubal Patency Assessment to the Gold Standard of Laparoscopy and Dye Testing
Conditions: Tubal Factor Infertility
Sponsor: Cairo University

                                                                                                          
 
 
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Title : 
Comparison of the diagnostic accuracy of Hysterosalpingo-lidocaine-foam 
sonography versus hysterosalpingography in tubal patency assessment to the 
gold standard of laparoscopy and dye testing 
 
 
Date: 1/5/2022 
 
 
 
NCT05419921 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                          
 
 
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Faculty of Medicine, Cairo University Postgraduate Research Program 
Template  
 
 
1- Study 
 
Title : 
Comparison of the diagnostic accuracy of Hysterosalpingo-lidocaine-foam 
sonography versus hysterosalpingography in tubal patency assessment to 
the gold standard of laparoscopy and dye testing 
Degree:   
Date of registration: May 2022 
 
    2.  Investigators : 
 
1-Mona Aboulghar Prof Obs & Gyn Cairo university 
     2-Mona Foad Assisstant Prof Obs & Gyn Cairo University 
3-Islam El Khatib Assistant Lecturer  Obs & Gyn New Giza University  
4-Shaimaa Mostafa Lecturer Obs & Gyn Cairo Univserity  
5-Yasmine Zakaria Medical Student Cairo University  

                                                                                                          
 
 
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3. Investigators: 
 
 
4. Background: 
 
Tubal disease accounts for 30-40% of female factors of infertility.(1) 
Therefore, tubal testing is an essential part of female infertility work-up.(2,3) 
Since falsely occluded tubes may lead to unnecessary interventions and falsely 
patent tubes may lead to unsuccessful in-vitro fertilization embryo transfer 
(IVF-ET) trials,(5,6) an accurate tubal test is an essential. 
 
laparoscopy with dye testing (LDT), i.e., laparoscopic chromopertubation, is 
the gold standard tubal patency test.(1,6,7) It is the recommended tubal test by 
the National Institute for Health and Clinical Excellence (NICE) and the 
European Society of Human Reproduction and Embryology (ESHRE) for 
women suspected to have tubal disease as it allows for direct visualization, 
diagnosis, and treatment of tubal and other pelvic pathologies.(3,8) However, 

                                                                                                          
 
 
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LDT is an invasive procedure requiring general anesthesia that can be 
associated with bleeding and visceral injury.(1,6,7,9)  
 
Hysterosalpingogram (HSG) has been reported to have sensitivity of 53% and 
specificity of 87% in the diagnosis of tubal block.(4) It has been the most 
commonly used initial tubal patency test as it offers a less-invasive and less-
expensive alternative to LDT.(6) However, HSG is associated with radiation 
exposure, pain, and allergy. It cannot diagnose myometrial or ovarian 
pathologies as well.(1,6,7,9) 
 
Hysterosalpingo-contrast sonography (HyCoSy) was introduced as a safer and 
less-painful alternative to HSG with comparable diagnostic accuracy and 
superiority in diagnosing uterine, ovarian, and myometrial 
pathologies.(1,6,9,10-12) HyCoSy is the recommended tubal test by NICE for 
women not known to have tubal disease, as an alternative to HSG, whenever 
appropriate expertise is available.(3) Air and saline use as contrast medium 
with HyCoSy made the procedure highly operator dependent.(1,6,13-16) 
Hyperechogenic and longer-lasting echogenic media then followed but are 
currently commercially unavailable or not approved for tubal testing.(1,6,14–
19) 
 

                                                                                                          
 
 
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In 2007, ExEm gel (GynaecologIQ, Delft, Netherlands) was introduced(20) and 
registered as European Confirmatory (CE) approved drug for tubal testing.(15) 
Hysterosalpingo-foam sonography (HyFoSy), using diluted ExEm gel foam, 
has been established as a safe, feasible, tolerable, and accurate alternative to 
HyCoSy and HSG that has been widely used in infertility 
clinics.(1,6,7,9,10,14,18,19,21–26) 
 
In 2017, hysterosalpingo-lidocaine-foam sonography combined with power 
doppler (HyLiFoSy-PD) was introduced as a cost effective and less painful 
possible alternative to HyFoSy that can be used whenever the contrast media is 
unavailable. “Flaming tube” sign, detected using power doppler (PD), was also 
described as to allow easier recognition of tubal patency.(27) Our study aims to 
compare the diagnostic accuracy of HyLiFoSy-PD with the most commonly 
used tubal test; HSG, with reference to the gold standard tubal test; laparoscopy 
and dye testing. 
 
5. Objective: 
 
The aim of this study is to evaluate the difference between the diagnostic 
accuracy 
of 
Hysterosalpingo-lidocaine-foam 
sonography 
and 
hysterosalpingography, with reference to the gold standard tubal test; 
laparoscopy with dye testing. 
   
6. Study Design: 
 
This will be a cross-sectional study 

                                                                                                          
 
 
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7. Scientific committee approval:  
 
 
8. Study methodology: 
Population of study, disease condition and setting: 
 
Women in the reproductive age group between 18- and 40-years old presenting 
with primary or secondary infertility who underwent  HSG in the previous 5 
years as a part of their infertility work-up with availability of good-quality HSG 
images, & did not get pregnant in this period, and gave no history of incidences 
that might affect their tubes, such as : abdominal surgery or laparoscopy, pelvic 
inflammatory disease, smoking, and intrauterine device insertion.  
 
Women fitting these inclusion criteria and scheduled for LDT as part of their 
infertility work up will be considered. HyLiFoSy-PD will be carried out few 
days before the already scheduled LDT.  
 
The study will be conducted in the Cairo fetal medicine unit, department of 
Obstetrics and gynecology, Cairo university. 
Inclusion criteria: 
1. Age group (18-40) 
2. Informed signed Written consent. 
3. Scheduled for LDT as a part of their infertility management  

                                                                                                          
 
 
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4. Have undergone HSG in the previous 5 years with the availability of 
good-quality HSG images. 
5. No incident factors that might have affected the tubal status after she 
underwent HSG within the previous 5 years, such as ; abdominal surgery 
or laparoscopy, pelvic inflammatory disease, smoking, and intrauterine 
device insertion.  
 
Exclusion criteria: 
Women with any of these factors will be excluded: 
 
1. LDT scheduled for a therapeutic purpose due to a known tubal or ovarian 
pathology 
2. Lack of good-quality HSG images. 
3. Withdrawal of consent. 
4. Using contraception 
5. Women outside reproductive age 
6. Known allergy to lidocaine 
7. Active pelvic inflammatory disease 
8. Undiagnosed genital tract bleeding. 
9. Evident tubal pathology (such as hydrosalpinx) or pregnancy diagnosed 
by transvaginal ultrasound (TV-US) prior to performing HyLiFoSy-PD  
 
Methodology in details 

                                                                                                          
 
 
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Interpretation of HSG results: 
 
Review of the HSG films will be done for assessment of the tubal patency; 
tubes will be considered patent if the dye is seen throughout their whole length 
and till their ends with a positive immediate spill or a spill in the delayed film. 
If the dye does not pass through one or both cornual ends, or if a part of the 
tube is seen filled with dye but not the whole length then tubal obstruction will 
be considered. Patients with hydrosalpinx seen by HSG are to be assessed first 
by US if no visible hydrosalpinx is seen by US and she has no signs of PID 
then she can proceed to the HyLiFoSy-PD procedure.  
 
Hysterosalpingo-lidocaine-foam sonography procedure: 
1. HyLiFoSy-PD procedure will be performed in proliferative phase of the 
cycle (Days 5 – 12).  
2. Clinical evaluation including history taking and a baseline two-
dimensional (2D) TV-US examination will be carried out prior to starting 
the HyLiFoSy-PD procedure.  
3. TV-US will be performed using a probe of frequency 4-9 MHz (Voluson 
E10 ® GE Healthcare). 
4. Administration of a non-Steroidal anti-inflammatory drug (NSAID) 
rectal suppository will be carried out one hour before the procedure 
(diclofenac sodium 100 mg), in addition to antibiotic prophylaxis using 

                                                                                                          
 
 
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oral azithromycin for 3 days, starting the day before the procedure and 
continued for one day afterwards 
5. In the dorsal lithotomy position, the cervix will be visualized with a 
Cusco speculum, cleaned with an antiseptic, then a 5- or 6- Fr pediatric 
Foley’s balloon catheter will be introduced into the cervical canal with 
the help of a Bozeman forceps and a tenaculum if necessary.  
6. The balloon will be positioned in the lower uterine cavity and inflated 
with 2 ml of saline to prevent backflow of contrast medium through the 
cervix, then the speculum will be removed. The TV-US probe will be 
reintroduced in a longitudinal plane to confirm correct placement of the 
catheter. 
7. The foam contrast agent will be created by mixing 3–4mL of 2% 
lidocaine gel (Xylocaine Jelly 2%, Atrazeneca, Sweden) with 16–17mL 
of saline. The assistant will create the foam immediately before 
application by shaking the mixture (approximately 10–20 times) between 
two connected syringes. This will be done until a whitish suspension is 
obtained. 
8. Repeated small doses (3-5 ml) of the lidocaine-made foam will be 
infused slowly into the uterine cavity while observing the flow of the 
contrast medium in each fallopian tube.  
9. Using greyscale US, flow over the whole length of the tube, fimbrial 
outflow, or peritoneal spillage of contrast will provide definite evidence 

                                                                                                          
 
 
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of tubal patency. Contrast filling of the uterine cavity without cornual 
flow will suggest tubal occlusion.  
10. PD will then be added to re-assess tubal patency and assess the “flaming 
tube” sign. Flaming sign interpretation will be classified as: strong, 
weak, or absent. 
11. Images will be stored as 2D and PD still images and video clips. 
HyLiFoSy-PD will be performed by experienced sonographers at our 
unit, who will be blinded to the results of LDT. 
12. Patients will be asked about the degree of discomfort or pain they felt 
during and immediately after the procedure. Using categorical verbal 
rating scale (VRS),(28) Procedure will be stopped if a patient 
experiences severe pain.  
13. Patients will be followed up overnight and monitored for any other 
procedure-related side effects or complications. 
14. Within a week following the HyLiFoSy-PD procedure, standard LDT 
will be carried out by experienced endoscopists who will be blinded to 
the results of HyLiFoSy-PD. During LDT, tubal patency will be tested 
using methylene blue dye. Tubal evaluation during LDT will be 
classified as: patent with immediate spill, patent with delayed spill, or 
blocked. 

                                                                                                          
 
 
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Possible Risk (mention if there is any risk or not) 
Side effects such as vasovagal reactions, allergic reaction, and venous 
intravasation have been reported in literature in hysterosalpingo-foam studies. 
However, in our previous hysterosalpingo-lidocaine-foam sonography study, 
none of these side effects were encountered. For the possible risk of infection, 
all patients will be given prophylactic antibiotics. In addition, any case with 
visible hydrosalpinx or signs or symptoms of PID on US prior to performing 
HyLiFoSy-PD will not perform the procedure. 
 
9. Study outcomes: 
Primary outcomes   
1. Diagnostic accuracy of HyLiFoSy and HSG with reference to LDT, in 
terms of sensitivity, specificity, positive predictive value, negative 
predictive value, and overall accuracy. 
 
Secondary outcome parameters 
1  -Diagnostic accuracy of adding power doppler to the HyLiFoSy.  
 
2-Evaluate the procedure associated pain  
3-Evaluate the procedure duration 
4-Percentage of failed or inconclusive attempts and possible reasons for 
that 
5-Incidence and rate of potential complications for example: vasovagal 
and allergic reactions, venous intravasation. 
 

                                                                                                          
 
 
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10.  Sample size: 
Using the following equation:(29) 
  
 
With power of the study 90%, CI 95%, average sensitivity of HSG is 0.55,(4) 
and sensitivity of  HyLiFoSy-PD is 90%,(30), prevalence of tubal pathology is 
30%,(1); 100 patients are required to fulfill the sample size. To compensate for 
any possible dropouts (5%), 5 more patients will be recruited. So, the total 
sample size will be 105. 
 
11. Statistical analysis: 
After recording and collecting the data, statistical analysis will be performed 
using the Statistical Package for the Social Sciences (SPSS, version 16.0, SPSS 
Inc, Chicago, Illinois, USA). Data will be statistically described in terms of 
mean and standard deviation if they were of normal distribution, and in terms 
of median and range if they were not normally distributed. Frequencies 
(number of cases) and percentages will be used when appropriate. Accuracy 
will be represented using the terms sensitivity, specificity, PPV, NPV, and 
overall accuracy. Testing the difference in the results of tests was done using 

                                                                                                          
 
 
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one-way analysis of variance (ANOVA) test. P-values less than 0.05 will be 
considered statistically significant.  
 
12. Source of funding: 
 
          Self-funding 
    
13. Time plan 
From 1/6/2022 – 1/6/2024 (2 years) 
 
14. References: 
 
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with laparoscopy and dye testing in tubal patency assessment in cases of 
infertility. Manuscript submitted for publication.