Hysteroscopic Evaluation of Fallopian Tubal Patency Compared to Laparoscopic Chromopertubation: a Prospective, Randomized Study on the "Flow" and "Parryscope" Techniques
Phase: NA
Conditions: Infertility of Tubal Origin, Infertility, Female, Fallopian Tube Occlusion, Uterus Abnormal
Sponsor: Medical University of Vienna

Hager Study protcol – Hysteroscopic Evaluation of Tubes 1.1 2019-08-27 
 
Study protocol 
 
Project title:  Hysteroscopic evaluation of Fallopian tubal patency 
compared to laparoscopic chromopertubation: a prospective, randomized 
study on the “flow” and “Parryscope” techniques 
Brief title:  Hysteroscopic evaluation of Fallopian tubal patency 
 
 
 
Participants: 
 
Investigator: 
Assoc.Prof. Priv.Doz. Johannes Ott 
 
Participating Doctors: 
Dr. Marlene Hager 
Assoc. Prof. Priv. Doz. Johannes Ott 
a.o.Univ. Prof. Dr. Christine Kurz 
 
Participating Clinics:  
 
 
Medical University of Vienna, Department of Obstetrics 
and Gynecology, Clinical Division of Gynecologic 
 
 
 
 
Endocrinology and Reproductive Medicine 
 
 
 
 
Spitalgasse 23 
 
 
A-1090 Vienna, Austria 
Tel: +43 - 1 - 40400 – 28160 
Fax: +43 – 1- 40400 – 28170 
 
 
 

Studienprotokoll_HSK-Flow_vs_Parryscope_V1.0_2019-03-27 
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Introduction and scientific background: 
 
Hysteroscopy is an important tool in the evaluation of sterility. [1-5] It allows direct visualization of 
the uterine cavity and enables the diagnosis of numerous pathologies, including endometrial 
polyps, intracavitary myomas and also more rare diseases associated with sterility and infertility, 
such as Asherman-syndrome and anomalies of the uterus itself. Hysteroscopy shows high reliability 
and is considered the gold standard for intrauterine evaluation [1-6]. 
 
When performing hysteroscopy, experts often assess the patency of the tubes via the visibility of 
flow of the hysteroscopic fluid going through the ostia of the tubes. In the recently published study 
“Assessment of tubal patency: A prospective comparison of diagnostic hysteroscopy and 
laparoscopic chromopertubation” it was demonstrated that visualizing contrasting substances 
disperse through the ostia is a significant and meaningful metric for tubal patency (sensitivity 85.2, 
95% CI: 76.1-91.9; specificity: 66.1, 95% CI: 52.2-78.2). This confirmed the value of this 
approach, consistent with our previous retrospective study on the same topic [7]. Nevertheless, it 
is important to mention that the prospective study showed both a lower specificity (66.1% vs. 
77.6%) and a lower positive predictive value (79.8% vs. 91.3%). 
 
Pre- and posthysteroscopic vaginal sonography for the evaluation of the hysteroscopic fluid in the 
pouch of Douglas [9,10], selective hysteroscopic pertubation of the tubes [11] and the visibility of 
air bubbles traversing through the Fallopian tube ostia after an air infusion into the uterine cavity 
[10,12] have been reported to be reliable methods for hysteroscopic tubal patency assessment. 
Particularly the last one, also called the “Parryscope technique”, named after its inventor, seems to 
be highly reliable, easy to conduct and clinically relevant [8,10,12]. The “Parryscope technique” 
reaches a sensitivity of min. 98.3% and a specificity of 83.7% [9] and, thus, seems to perform 
even better than the technique evaluating the “tubal flow”. 
 
Assessing tubal patency during hysteroscopy is highly relevant, particularly when it allows for a low 
cost, fast, gentle, and accurate way of gathering information that may guide clinical care. 
Therefore, it is important to know which of the above-mentioned techniques is the best. This 
prospective randomized study aims to compare the hysteroscopic assessment of the tubes via 
“tubal flow” [7] and the “Parryscope technique” [10,12]. At our department, the Clinical Division of 
Gynecological Endocrinology and Reproductive Medicine of the Medical University of Vienna, a 
diagnostic hysteroscopy is usually performed directly before every infertility-related laparoscopy. 
These operations are always performed by an expert in the field of reproductive surgery, which 
should guarantee a good clinical quality of our data set. 
 
Study aims: 
The primary aim of this study is to evaluate the relalibilty of (1.) the hysteroscopic visualization of 
a “tubal flow” and (2.) the “Parryscope technique” as compared to the gold standard, namely 
laparoscopic chromopertubation. 
 
 

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Study hypothesis: 
 
Null hypothesis: The hysteroscopically visualizable „tubal flow“ and the „Parryscope technique“ are 
similarly reliable in the evaluation of tubal patency. 
 
Alternative hypothesis: The hysteroscopically visualizable „tubal flow“ shows a lower sensitivity and 
specificity than the „Parryscope technique“ for the evaluation of tubal patency. 
 
 
Study design:  
Prospective, randomized study. 
 
Participants: 
Inclusion criteria:  
- 
The patient is subfertile, defined as being unable to become pregnant within a year despite 
unprotected sexual intercourse. It is also within the standard of care to be presumed 
subfertile if one has tried for six months and has known risk factors that would hinder 
conception, including but not limited to anovulation and endometriosis. 
- 
A concurrent diagnostic hysteroscopy and laparoscopy with chromopertubation are 
performed at the Clinical Division of Gynecological Endocrinology and Reproductive 
Medicine at the Medical University of Vienna. 
- 
The patient has given her written informed consent after detailed information on the study 
by medical professionals at the Department of Obstetrics and Gynecology of the Medical 
University of Vienna.  
- 
The patient is 18 and 45 years old. 
 
Exclusion criteria:  
- 
The patient had a tubectomy on one or both sides. 
- 
There is no “informed consent”. 
- 
The patients has active vaginal infection or other conditions that would preclude 
hysteroscopy. 
 
Primary Outcome Parameters: 
Hysteroscopic evaluation of tubal patency (either by a positive “tubal flow” or a visible flow of air 
bubbles in the “Parryscope technique”) and the result of the laparoscopic chromopertubation (tubal 
patency existing or not existing). 
 
Secondary Outcome Parameters: 
For the descriptive analysis, several hysteroscopically visualizable additional parameters will be 
evaluated: (i) existence of any hysteroscopic abnormalities (including endometrial polyps, myomas, 
adhesions, anomalies or cervical stenosis). (ii) characteristics of the tubal “flow” – clearly 
visualizable or questionable, visualization of air bubbles and/or floating structures in the cavity. (iii) 
clarity of the hysteroscopic view (clear versus hazy). 

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Recruitment: 
Women will be invited to participate by medical professionals at the Department of Obstetrics and 
Gynecology of the Medical University of Vienna using the above-mentioned criteria in the course of 
their admission to the ward one day before surgery. Potential participants are informed about the 
procedure, clinical relevance and the balance of risk and benefits incurred through study 
participation. Patients willing to participate will express this through written affirmation (a “consent 
form”). 
 
Parameters obtained: 
The following parameters will be collected and included in the database. They do not require 
additional effort on behalf of the patients. All data will be obtained using the study-specific case 
report form and will be entered into a SPSS database in a semi-anonymized manner.  
 
- 
Patient’s age 
- 
Body mass index 
- 
Primary/secondary subfertility 
- 
Obstetrical history (gravidity, parity) 
- 
History of risk factors relating to tubal disease (chlamydia infection, endometriosis, etc.) 
- 
Detailed information about the indication for surgery 
- 
Main outcome parameter 1: Hysteroscopic findings: tubal patency assumed or not assumed 
in right/left tubal ostium (information provided separately for each side) 
- 
Additional findings: any hysteroscopic abnormalities (including endometrium polyps, 
myomas, adhesions, anomalies or cervical stenosis). In the “tubal flow” group an additional 
finding would also be the presence of air bubbles. Moreover, the clarity of the hysteroscopic 
view will be evaluated (clear versus hazy). 
- 
Duration of the hysteroscopic evaluation of tubal patency (in minutes). 
- 
Additional interventions: Curettage and operative hysteroscopy. 
- 
Uterine length. 
- 
Main outcome parameter 2: Laparoscopic findings: tubal patency as assessed by 
chromopertubation (information provided separately for each side)  
- 
Amount of blue dye used in chromopertubation 
- 
Performance of any additional laparoscopic interventions during the operation  
- 
A 
subjective 
assessment 
of 
pressure 
used 
in 
demonstrating 
patency 
with 
chromopertubation (low vs high, which affects accuracy and prognosis) 
 
The additional data acquisition will be conducted to give an exact characterization of the patient 
population to allow a comparison with the published literature. 
 
Techniques of hysteroscopic evaluation of tubal patency: 
“Tubal flow”-group: a positive “flow” is defined as the observation of saline directly traversing the 
ostia, endometrial structures floating toward the ostia, or air bubbles traversing the ostia. 

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“Parryscope”-group: A small amount of air is introduced into the iv tubing by inverting the drip 
chamber to create air bubbles. When air enters the uterine cavity, a single large air bubble or 
stream of air bubbles traversing the ostia is considered indicative of tubal patency. At least 10 
seconds of intracavitary evaluation is typically performed before air bubble entry to allow pressure 
equilibration if a hydrosalpinx is present [10]. At least 30 seconds of observation per ostia is 
performed if patency is not observed. 
 
Additional considerations: 
1. Since in the “flow”-group air bubbles might develop spontaneously and, thus, should be 
assessed, conducting the “Parryscope”-technique is only possible after the evaluation of the 
tubal flow. 
2. Reactive tubal spasms could occur especially during a prolonged hysteroscopy. 
3. This is why in one particular patient only one technique should be performed. 
 
Sample size calculation: 
The calculation is based upon the following considerations: 
1. Direct comparison of the two groups is not possible. Hence, separate evaluation of the two 
methods will be performed. Evaluating both methods in one particular patient in the course 
of a single intervention is impossible without a mutual interference (see: “Additional 
considerations” above). 
2. The “flow effect” is considered the less reliable method and thus, the sample size was 
aligned to this method. An odds ratio of approximately 10, an alpha of 5%, a power of 
80%, a general disease likelihood of 39% and a sensitivity of 66% for occluded tubes result 
in a total amount of 59 tubes and, accordingly, 30 patients. 
3. Thus, the group for the “Parryscope”-technique should also contain 59 tubes (= 30 
patients). 
4. The randomization of the total 60 patients is performed as block randomization in 4 blocks 
via the software “R”. 
 
Statistical analysis: 
Numerical data (age, body mass index) will be reported as mean and standard deviations, nominal 
variables (primary/secondary sterility, indication for the reproductive medical intervention, visibility 
of the “flow” in the left and right tubal ostium, pathologies in the uterine cavity in the 
hysteroscopy, patency of the tubes via chromopertubation, information about further laparoscopic 
interventions during the operation) as number and frequency. The McNemar Test will be used for 
the calculation of the reliability of the hysteroscopic assessment of the tubes. The sensitivity, 
specificity, positive and negative predictive values will be provided including the according 95% 
confidence intervals (95% CI) for both study groups (evaluated technique versus gold standard 
laparoscopic chromopertubation). The according odds ratio is over 10 will be evaluated by the use 
of a binary logistic regression model. Statistical analyses were performed with the software “R”. 
Differences were considered significant if p<0.05. 
 
Data quality evaluation: 

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Extreme values will be double-checked. In addition, random checks by two independent 
investigators will be conducted to ensure the accuracy of our data. 
 
Risk-benefit-analysis: 
In this prospective study, no further data acquisitions, follow-up examinations or surveys will be 
necessary. Except from the above-mentioned additional findings during the interventions, the only 
additional data to be collected would already be inherently obtained as part of procreative 
evaluation. Accordingly, if patients would be undergoing the described interventions (hysteroscopy, 
laparoscopy) independent of their choice to participate, this should not shift cost or risk for them. 
Additionally, since the study evaluations are minimal risk (visual observation of natural 
intracavitary flow patterns and deliberate addition of 0.5 mL of air in to saline during hysteroscopy 
(where greater amounts routinely enter the uterus accidentally through how lines are primed), 
safety should remain high. The analysis and publication of the data will be done with patient 
deidentification. 
 
Agreement on the access of the principle investigator: 
The principle investigator will have access to all study documents and statistics at all times. 
 

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