DOI:
Original papers
Comparison of Hystero-salpingography and Hysterosalpingo- Contrast Sonography for tubal patency testing: technical success, pain perception, side effects and complications
Anita Roxana Maxim
1,2, Ovidiu Horia Gligor
1, Radu Ion Badea
2,31Polisano Clinical Hospital, Sibiu, 2“Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca,
3“Prof. Dr. Octavian Fodor”Regional Institute of Hepatology and Gastroenterology, Cluj-Napoca, Romania
Received 25.08.2020 Accepted 04.02.2021 Med Ultrason
2021, Vol. 23, No 3, 283-288
Corresponding author: Anita Roxana Maxim
Polisano Clinical Hospital Sibiu,
1A Izvorului street, 550172 Sibiu, Romania Phone: +40786112200
E-mail: [email protected]
Introduction
The initial infertility workup requires reproducible, diagnostically accurate, minimally invasive and cost-ef- fective approach. The first evaluation plays a major role in the future recommendations for assisted reproduction techniques such as intrauterine insemination or in vitro fertilization. Out of the couples addressing a fertility
center, 14% require treatment for uterine or tubal pathol- ogy [1]. For this reason, assessment of tubal patency and normal uterine cavity is the first-step examination in the morphological evaluation of infertile women.
Assessing the anatomy of the female reproductive organs involves complex diagnostic modalities, some of them being invasive, adding up to significant psycho- logical distress in a particularly burdening patient situa- tion. Currently, laparoscopy with chromopertubation is considered the gold standard test for tubal assessment, completed by hysteroscopic examination of the uterus.
This approach, however, is not feasible as the first line evaluation due to high costs and potential surgical com- plications [2,3].
In some fertility centers, radiologic hysterosalpingog- raphy (HSG) is the method of choice for tubal and uterine Abstract
Aims: The aim of this study was to compare technical success and tolerability between hysterosalpingography (HSG) and hysterosalpingo-contrast ultrasonography (HyCoUs) as a first-line evaluation method in a single fertility center. Mate- rial and methods: The study included 56 infertile women: 27 patients underwent HSG and 29 patients underwent HyCoUs.
Pain perception was measured by means of an 11-point visual analog scale (VAS) and the Stacy score. Side-effects, technical aspects, complications and variable correlations were documented. Results: The median VAS scale was 5 (4;6) for HSG and 1 (1;2) for HyCoUs. The median Stacy score was 2 (1;3) for HSG and 1 (0;1) for HyCoUs. The difference in pain perception was statistically significant for both pain scores (p<0.001). All patients undergoing HyCoUs reported a visual analog (VAS) pain score of <5 and 59.3% of patients undergoing an HSG reported a score of >5. Increased pain scores showed a statistically significant association with duration and total volume of substance infused. The type of procedure and volume infused were independently associated with the VAS scale. In the HSG group, 14.8% (4) of patients reported a vagal effect (p<0.001), one patient requiring hospitalization. No vagal effects were reported following HyCoUs and the method was technically successful in 100% (29) of cases. HSG was successful in 88.9% (24) of cases. Conclusions: HyCoUs is a well-tolerated procedure with reduced frequency of adverse effects. Low pain perception is strongly correlated with a low volume infused. It is non-invasive and efficient in rendering good quality images.
Keywords: Hysterosalpingography; tubal obstruction; pain perception; infertility; hysterosalpingo-contrast ultrasonog- raphy
DOI: 10.11152/mu-2692
patency evaluation, even though it has some clear limita- tions such as atopic phenomena triggered by the contrast agents used, no real time examination of the pelvic or- gans and the use of ionizing radiation [4].
Ultrasound (US) is an increasingly preferred imag- ing technique for infertility evaluation in women [5].
Two-dimensional (2D) vaginal US is the first tool used for investigating the uterus, adnexa and ovaries. It can be performed in an outpatient setting, during the initial consultation [6]. Acquisition of a three-dimensional (3D) volume offers a complete examination of the shape of the uterus and ovarian follicle count [7].
Hysterosalpingo-contrast ultrasonography (HyCoUs) is an US examination of the uterus and Fallopian tubes which allows the assessment of tubal patency by means of a transcervical contrast agent (air-saline or micro bub- ble contrast agents) [8,9]. Several studies have shown that HyCoUs displays high specificity and sensitivity for tubal and uterine cavity assessment [10-16]. On the other hand, there is a high variation in protocols (timing, duration, contrast medium, volume infused) and limited evidence on patient tolerability and actual complications rates [17,18].
For this reason, the aim of this prospective study was to compare technical success and tolerability between HSG and HyCoUs.
Material and methods
A prospective, interventional, analytical, case-control study, including 56 patients from the Polisano Fertility Center, Sibiu, Romania was conducted between January 2018 and May 2019. The institutional Ethics Commit- tee approved the study and all participants signed an in- formed consent form.
Inclusion criteria were: female patients aged between 18-40 years with a history of infertility, previously unin- vestigated for uterine or tubal anomalies, presenting to the fertility center for an initial diagnostic work-up. All patients were required to have a normal cervical cytol- ogy within the last 6 months and negative bacteriology testing from the cervix in the last 3 months. Exclusion criteria were history of infertility of less than one-year, abnormal vaginal bleeding, acute pelvic infections and genital malignancies. In figure 1 the selection process of the patients is detailed. A total of 56 patients were rand- omized by means of a sealed envelope system. Women in both groups did not receive any pain medication before undergoing the procedure and no antibiotic therapy was prescribed. Verbal anesthesia was used in all cases, with extensive patient counseling before all procedures, includ- ing visual aids explaining the examinations in detail [19].
All procedures, both HSG and HyCoUs, were per- formed by the same practitioner, an obstetrics-gynecolo- gy specialist with more than 5 years of experience.
HSGs were performed at the institution’s radiology unit within the first 12 days of the menstrual cycle. The HSG was performed as follows: the cervix was exposed with a speculum and, after local disinfection, a Pozzi cer- vical tenaculum was applied. After attaching a Schulze salpingogram cannula, the speculum was removed and the ioversol solution (Optiray 350, 741mg/ml, Guerbet) slowly injected under radioscopic guidance. A total of 2 radiographic images were taken - first after injecting 5-10 ml of contrast to check for uterine cavity and cor- rect positioning of the cannula and the second 20 minutes after the beginning of the procedure to check for passage of the contrast medium through the Fallopian tubes into the peritoneum. After injecting the contrast medium and obtaining a satisfactory image of the uterus and tubes, the tenaculum and canula were removed for patient comfort until the last radiographic image was acquired. The dura- tion of each procedure and the volume of contrast needed in each case to acquire good quality images were also documented.
The HyCoUs examinations were performed using a Samsung WS80A machine with 2D/3D/4D/contrast en- hanced US (CEUS) software and endocavity transvagi- nal transducer. Routine 2D transvaginal examination of the uterus, endometrium, ovaries and Douglas pouch was initially done, scanning for any morphological ab- normalities and also localizing the interstitial part of the salpinges before injecting the contrast medium followed by a 3D volume acquisition of the uterus (fig 2).
Then, the cervix was exposed with a single-use vagi- nal speculum, disinfected with ethanol and a single-use Labotect 3-way balloon catheter was introduced inside the uterine cavity through the cervical os. The catheter was fixed inside the uterus by filling the balloon with 2 ml of air and then the vaginal speculum was removed.
The CEUS examination was performed using SonoVue, (Bracco, Milan Italy) undiluted contrast medium: 5 ml of substance was slowly injected through the catheter while performing a full transvaginal scan of the uterine cavity Fig 1. Flow chart with selection process of the patients
and tubes (fig 3). At the end of the procedure, the balloon was deflated and the catheter removed.
Immediately after either procedure, the patients were questioned about the pain experienced using an 11-point visual analog numerical rating scale (VAS) where 0 rep- resents no pain at all and 10 severe pain. The pain caused by the procedures in comparison to menstrual pain was also assessed (Stacy score) where 0 was no reaction or discomfort, 1 - slight pain less than menstrual pain, 2 - moderate pain, exceeding menstrual cramps but no vagal effects, 3 - vagal effects or pain requiring hospital obser- vation, 4 - vagal effects or pain requiring resuscitation [20]. The vagal effects consisted of nausea and/or vom- iting, dizziness, syncope, hypotension and bradycardia.
The frequency of difficult examinations was docu- mented in both groups, such as impossible catheter pas- sage or lack of satisfactory visualization of the uterus and/or Fallopian tubes, resulting in rates of technical suc- cess for each respective examination method.
Statistical analysis
Statistical analysis was carried out using the MedCalc Statistical Software version 19.1.5 (MedCalc Software bv, Ostend, Belgium; https://www.medcalc.org; 2020).
Median and 25-75 percentiles were used to describe the quantitative variables and frequencies and percentages for nominal variables. Between-group comparisons were performed using the Man-Whitney test for quantitative variables and the chi-square tests or Fisher’s exact test, for nominal variables. Spearman’s rho was used to test the correlation between quantitative variables. A multiple linear regression was used in order to find out which vari- ables were independently associated with the pain score.
VAS scale values were logarithmically transformed in or- der to normalize the distribution. Variables that achieved a p<0.2 in the univariate analysis, were introduced in the multivariate analysis. A p value <0.05 was considered statistically significant.
Results
The 56 patients were randomized by means of a sealed envelope system: 29 underwent a HyCoUs (group 1) and 27 underwent HSG (group 2). There was no significant difference between the two groups concerning the age, infertility duration or the days of menstrual cycle when the procedure was performed. The pain appreciated on VAS and Stacy score and the volume infused were higher in the second group but the duration of the procedure was longer in the first group (all p<0.001) (Table I).
No significant technical difficulties or incidents oc- curred during the HyCoUs. HSG vagal effects were re- ported in 14.8% of cases (p<0.001). The detection fre- quency for unilateral or bilateral salpinges obstruction has no significant differences between the two groups (p>0.05) (Table II).
Tables III and IV show the association between sever- al variables and the reported pain intensity on VAS scale.
Statistically significant correlations were found between VAS and duration of procedure or infused volume. Pa- tients with vagal effects experience significantly worse pain.
In order to find out which variables were indepen- dently associated with the pain we used the multiple lin- Fig 2. Transvaginal 3D ultrasonography volume acquisition of
the uterine cavity
Fig 3. Transvaginal contrast enhanced ultrasonography: a) sagittal view of the uterine cavity; b) view of the Fallopian tube with contrast passage; c) view of the periovarian spill of contrast after tubal passage
ear regression (table V). The type of the procedure and the volume infused were independently associated with the VAS scale.
Discussion
Few studies have focused on patient compliancy to the ultrasound method in comparison to other investiga- tions such as HSG. The current study focuses on pain perception, technical aspects and complications of the two methods. Our data showed that HyCoUs is a well- tolerated examination with a low rate of complications and side effects. We found statistically significant differ- ence in pain perception by VAS and Stacy score, in favor of HyCoUs. Our results complement the results reported by Savelli et al [21] in a prospective study; the authors re- ported a mean numeric rating scale of the pain of 2.7±2.5.
Ayada et al compared HyCoUs to conventional HSG regarding the tolerability of the procedure [22]. Sixty-six patients with infertility underwent one of the two proce- dures and the authors reported no significant difference in procedure time, volume of contrast infused, patient
tolerability or adverse effects. We found significant dif- ference in the duration of the procedure between the two techniques, HyCoUs needing longer time. This might be explained in a subjective manner related to the experi- ence of the physician performing the examinations but is also related to the different equipment used.
In the study of Socolov et al, the authors reported a higher pain score for HyCoUs with no correlations be- tween pain intensity on the analog/digital scale and any of the variables analyzed [23]. We, however, found sig- nificant correlation between the volumes of contrast in- fused and pain intensity, as well as a significant inverse relation between the duration of procedure and pain score. In our study, for the HyCoUs procedure, we used maximum 5 mL of SonoVue compared to a maximum of 10 mL of ioversol contrast for HSG, which rendered suf- ficient information to document tubal patency and uterine cavity morphology with minimum discomfort for the pa- tient. The difference in amount of contrast infused could explain the higher pain score reported by patients in the Table III. Pain score correlations
Variable VAS*
r P
Age (years) 0.176 0.1
Duration of infertility (years) 0.028 0.8 Days of menstrual cycle 0.162 0.2 Duration of procedure (min) -0.415 0.001
Volume infused (ml) 0.792 <0.001
*VAS – visual analog scale
Table IV. VAS association with adverse effects and conditions
Variable VAS* P
Vagal effect Yes 6.5 (3.5; 8.75) 0.02 No 3 (1; 4.75)
Failed attempt Yes 5 (3; 5) 0.1
No 3 (1; 5)
Unilateral obstruction Yes 3 (1.75; 5.75) 0.6 No 3 (1; 5)
Bilateral obstruction Yes 4 (2; 5) 0.3 No 3 (1; 5)
*VAS – visual analog score Table II. Adverse effects, technical difficulties and tubal obstruction in study groups
Variable HyCoUs (n=29) HSG (n=27) P
Vagal effects 0 (0) 4 (14.8) <0.001
Failed attempt 0 (0) 3 (11.1) 0.1
Unilateral obstruction 3 (10.3) 3 (11.1) 1
Bilateral obstruction 2 (6.9) 5 (18.5) 0.2
The results are expressed as number (%); HyCoUs – hysterosalpingo contrast sonography; HSG – hysterosalpingography; n – number Table I. Clinical features, procedure timing, mean pain scores and technical aspects
Variable HyCoUs (n=29) HSG (n=27) P
Age (years) 31 (27.5;35) 34 (30;36) 0.1
Duration of infertility (years) 3 (2;5) 3 (2;5) 0.9
Days of menstrual cycle 9 (8;10) 9 (8;10) 0.5
Visual analog pain score 1 (1;2) 5 (4;6) <0.001
Stacy score 1 (0;1) 2 (1;3) <0.001
Duration of procedure (minutes) 20 (15;22.5) 10 (10;10) <0.001
Volumes infused (mL) 5 (5;5) 10 (10;10) <0.001
The results are expressed as mean (low;high); HyCoUs – hysterosalpingo contrast sonography; HSG – hysterosalpingography; n – number
Socolov et al study. The Sono Vue microbubble contrast agent generates a stronger acoustic signal compared to the air in the saline agent used in the Socolov et al study and could explain the different results. Also, the sealing of the cervical os with the inflated catheter balloon re- duces leakage of the substance outside the salpinges and uterus towards the vaginal canal. Using this equipment adds up to a longer duration of the HyCoUs but reduc- es the volume necessary for performing the examination and results in lower pain scores.
Regarding adverse effects of the two procedures, for HSG we report 4 (14.8%) cases of vagal effects and 3 (11.1%) cases of failed passage attempts. HyCoUs, how- ever, was well toleratedwith no vagal reactions or post- procedural complications. We were able to canulate the uterine cavity in all cases. Hamed et al [24] reported a low global rate of vagal effects (5.7%) and Savelli et al [21] reported a rate of 4.1% mild vagal effects in patients undergoing HyCoUs.
The difference in technical difficulties and complica- tions is possibly related to the different instruments used in our center. The HyCoUs canula that we use is similar to those used in intrauterine insemination procedures and is more malleable. The rigid Schulze canula used in oth- er centers that perform HSG offers less maneuverability, less precision in difficult patients (obese, nulliparas) and more pain when applied [25].
The findings of this study have to be seen in light of some limitations, one of them regarding the instruments used. The two procedures were not performed using the same type of uterine cannula. We attempted to use the flexible HyCoUs canula for HSG as well but this poses a lot of difficulty because HSG does not offer real time positioning of the canula. This leads to inconclusive examinations, repeated manipulation of the cervix and more discomfort for the patient [26]. Another limitation of our study is the sample size, though representative for the studied population, results could benefit from a larger cohort of patients. This would allow for more extensive
variable correlations regarding technical difficulties and adverse effects of the two procedures. Also, all of the examinations were performed by the same examiner, an infertility specialist from our center.
A longitudinal approach to the study population could offer valuable data regarding benefits of either examina- tion techniques in obtaining pregnancy. Few studies have focused on rates of spontaneous pregnancy obtained af- ter tubal patency testing as a result of contrast passage through the salpinges.
We consider that extensive counseling patients un- derwent before the procedures played an important role in reducing pain perception and stress-related discomfort during the examinations. Patients were kept informed about every step of the investigation before and during HSG/HyCoUs and were advised about the nature of the discomfort they might feel. Verbal anesthesia is carried out before and during the procedure and is aimed at es- tablishing a calm and familiar environment for the patient by means of conversation steering their attention away from the uncomfortable moments experienced during the intervention. It is a relaxation technique widely used for in-office minimally invasive procedures and significantly reduces the need for pain medication.
Further studies are required with a larger patient sam- ple size that would enable us to establish a complete in-of- fice examination protocol for pelvic anatomy performed in a single-visit concomitant to the HyCoUs that would be suitable as a first-line evaluation in a fertility center.
In conclusion, HyCoUs is a well-tolerated procedure with low rates of adverse effects and low pain perception.
Volume of contrast agent infused correlates independent- ly with pain perception. HyCoUs is safe, non-invasive and efficient in rendering good quality images regarding pelvic morphology in infertile patients. Therefore, the technique could be used as a first line evaluation meth- od in an office setting for women undergoing infertility treatment.
Conflict of interest: none Table V. Multiple linear regression for VAS
Unstandardized coefficients t P 95%CI for B*
B Std. Error Min Max
(Constant) -0.113 0.222 -0.509 0.6 -0.559 0.334
HSG 0.358 0.093 3.836 <0.001 0.170 0.546
Age 0.000 0.006 0.079 0.9 -0.011 0.012
Duration of procedure (min) 0.008 0.006 1.308 0.1 -0.004 0.020
Volume infused 0.029 0.012 2.447 0.01 0.005 0.052
Vagal effect 0.069 0.129 0.534 0.5 -0.191 0.329
Failed attempt -0.026 0.154 -0.168 0.8 -0.335 0.284
*B – regression coeficient
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