A New Red Flag Classification to Predict Vasovagal Syncope During Office Hysteroscopy: A Cross-Sectional Pilot Feasibility Study
Conditions: Vasovagal Syncope (VVS)
Sponsor: Tanvir Hospital

A New Red Flag Classification 
to Predict Vasovagal Syncope 
During Office Hysteroscopy: 
A Cross-Sectional Pilot 
Feasibility Study 
Updated date :   
13/6/2025
IRB No :    
 TH/IEC/BHR/
0154/2025/
TNV/P1/V4 
Hospital Name: 
Tanvir Hospital 

A New Red Flag Classification to Predict Vasovagal Syncope During Office Hysteroscopy: A 
Cross-Sectional Pilot Feasibility Study 
Rationale 
Office hysteroscopy is increasingly utilized due to advancements in instrumentation and techniques; 
however, its adoption in routine gynecologic practice remains limited to 10–12% of cases【1,2】. 
This under utilization is largely attributed to the perception of pain and lack of financial incentives. 
Consequently, fewer than 20% of gynecologists employ office hysteroscopy for the evaluation of 
intrauterine pathology【3,4】.
Although generally safe, vasovagal syncope (VVS) is the most concerning complication, with a 
reported prevalence ranging from 0.21% to 1.85%【5–9】. Other complications include pain, 
infection, and bleeding【10】. Surgeons often fail to anticipate vasovagal responses during the 
procedure. This study aims to develop a red flag classification system based on pain response to 
enable early recognition and prevention of VVS during office hysteroscopy.
Specific Aim 
To evaluate the feasibility of a predictive red flag classification system for identifying patients at 
risk of vasovagal syncope during office hysteroscopy, with the goal of enhancing procedural safety.
Background & Significance  
Vasovagal syncope, classified by the European Society of Cardiology as a form of reflex or neurally 
mediated syncope, is triggered either orthostatically or emotionally—commonly due to fear, pain 
(somatic or visceral), instrumentation, or blood phobia【11】. It manifests as hypotension, 
bradycardia, and transient loss of consciousness【12】. Reported incidences vary from 0% to 
4%【13–20.
Presyncope or vasovagal reaction is characterized by lightheadedness, palpitations, weakness, 
nausea, visual disturbances, and sweating. Beyond immediate risks, the consequences include 
premature procedure termination and increased patient anxiety. Physiologically, VVS is attributed 
to parasympathetic overactivation, especially during cervical manipulation, leading to a cascade of 
bradycardia, reduced vascular resistance, hypotension, and cerebral hypoperfusion【21】.
The Bezold–Jarisch reflex further explains VVS pathophysiology, involving baroreceptor-mediated 
inhibition of sympathetic tone and enhanced vagal activation【22】. Rigid hysteroscopes and the 
use of CO₂ as a distension medium increase the risk of vasovagal events【23】.
Key risk factors include a prior history of vasovagal reactions, age under 65, and high pre-
procedure pain scores【12】. VVS is 1.5 times more common in women, potentially due to 
physiological differences such as lower body mass index【24,25】.

The proposed classification aims to identify patients with lower pain tolerance likely to experience 
VVS, enabling timely preventive strategies.
Preliminary Data: 
Prof. Sergio Haimovich, Head of Reproductive Surgery at Embriogyn Clinic (Spain), has conducted 
over 5,000 office hysteroscopies in the past seven years, with only one case of syncope reported, 
linked to a myocardial infarction in a 75-year-old. This emphasizes the rarity yet potential severity 
of VVS.
Research design  
This is a multicenter, cross-sectional, analytical pilot study enrolling women undergoing office 
hysteroscopy over 12 months. Ethics approval and informed consent will be obtained at all 
participating centers.
In office hysteroscopy, we will utilize 1.9–2.9 mm hysteroscopes (primarily Bettocchi type) by the 
technique of vaginoscopy, without anesthesia or up to level 3a analgesia, in accordance with 
international consensus recommendations【26】. The choice of distension medium and 
hysteroscope is left to the operator's discretion. A nurse positioned at the head of the patient will 
record signs and symptoms of VVR/VVS.
Data Collection
Variables collected:
•
Demographics and clinical history (age, sexual active, parity, history of smoking, fasting 
status, history of dilatation & curettage, menopausal status, comorbid conditions, prior 
cesarean, prior cervical surgery, prior obstetric trauma ( such as severe perineal tears), use of 
preoperative analgesics, use of preoperative anti-anxiolytics, experience of the surgeon (< 
10 yrs or > 10 yrs of practice) is recorded. 
•
Weight in kilograms, height in meters will be combined to report body mass index (BMI) in 
kg/m^2. Time Frame: BMI is calculated when the women is enrolled in the study to perform 
office hysteroscopy.
•
Procedure-related factors (hysteroscopy procedure, level of pain management, type/size of 
instrument, type of fluid media used, use of fluid management system, use of gravity system, 
i.e. hydrostatic pressure, cervical stenosis, procedure time) is recorded.
•
Hemodynamic parameters (pre- and post-procedural blood pressure and pulse) are recorded.
•
Vasovagal symptoms and signs (sweating, nausea, hypotension, bradycardia, syncope) are 
noted during the procedure.
•
Tolerance level is recorded post-procedure by an independent nurse (not involved in the 
hysteroscopy procedure) using the red flag classification. Time Frame: From the initiation of 

the office hysteroscopy procedure until the completion of the surgery or the documentation 
of a vasovagal attack/syncope, assessed for up to 30 minutes.
•
Visual analogue score for pain (VAS - P ) is independently assessed post procedure by the 
nurse (not as a part of tolerance score), with zero described as no pain to 10 described a 
worst possible pain. Time Frame: From the initiation of the office hysteroscopy procedure 
until the completion of the surgery or the documentation of a vasovagal attack/syncope, 
assessed for up to 30 minutes.
Routine intraoperative blood pressure/pulse will not be recorded to avoid patient distress that may 
artificially trigger VVS.
 Clinical symptoms include excessive sweating, feeling of warmth, nausea, malaise, weakness, 
abdominal cramps, hyperventilation, and lightheadedness. Clinical signs include systolic blood 
pressure < 80 mm Hg and pulse rate < 60 bpm, facial pallor, and loss of consciousness.
Red Flag Classification
Normal menstruation is when the pain during periods does not interfere with daily activities. The 
level of pain tolerated by the women in relation to the menstruation is described as a green flag 
indicating well tolerated or tolerated, or red flag indicating not tolerated. 
Note: Patient request to stop the procedure at any level = Red Flag.
 
Flowchart  
 
 
 
Level
Description
Classification
0
Pain ≤ normal menstruation (Well tolerated)
Green Flag
1
Pain > menstruation, no signs of distress (Tolerated)
Green Flag
2
Level 1 + objective signs (sweating, pallor, malaise) 
(Tolerated)
Red Flag
3
Level 2 + facial pallor ± loss of consciousness (Not tolerated)
Red Flag
Patient enrôllement 
Baseline vitals recorded 

 
 
 
 
 
 
 
Inclusion Criteria
•
Women ≥18 years
•
Prior gynecological care
•
Informed consent provided
Exclusion Criteria
•
Inability to consent
•
Psychiatric disorders or anxiolytic use
•
Use of dilators or anesthesia above level 3a
•
Family history of VVS
Sample Size Calculation
Based on an estimated VVS rate of 6.3%【27】, and using a 95% confidence interval, the sample 
size of 46 was calculated using Crutzen’s online tool【28】.
Statistical Analysis
Descriptive analysis will be conducted for continuous and categorical variables. Chi-square tests 
will evaluate the association between pain classification and vasovagal events. The STROBE 
checklist will guide reporting.
Office hysteroscopy performed 
Intraoperative  VVR/VVS signs documents 
Post procedure vitals and tolerance score 
assessed
Data Analysis 

Primary Outcome
To assess feasibility in implementing the red flag classification system, as preparation for a future 
large-scale validation study.
Secondary outcome 
Potential barriers in implementing the red flag classification system, as preparation for a future 
large-scale validation study
Pre- specified outcome 
To measure visual analogue score for pain post procedure separately from the tolerance score.
To measure the body mass index of participant undergoing office hysteroscopy.    
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