Invest Clin 64(3): 317 - 328, 2023 https://doi.org/10.54817/IC.v64n3a5

Corresponding author: Xueniu Yang. NHC Key Laboratory of Birth Defects and Reproductive Health (Chongqing

Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and

Technology Research Institute), Chongqing, China. Email: ixkyko1967939@163.com

Clinical value of four-dimensional

hysterosalpingo-contrast sonography

assisted by intrauterine pressure

measurement for tubal patency evaluation.

Chunhong Lin

, Jianyong Chen

, Xianguo Li

, Linlin Wang

, Fengqin Yan

Ye Chang

, and Xueniu Yang

Third Department of Ultrasound, Hengshui People’s Hospital, Hengshui, Hebei

Province, China.

Department of Medical Medicine, Hubei College of Chinese Medicine, Jingzhou,

Hubei Province.

Medical Department, The Fifth People’s Hospital of Hengshui, Hengshui, Hebei

Province, China.

First Department of Ultrasound, Hengshui People’s Hospital, Hengshui, Hebei

Province, China.

NHC Key Laboratory of Birth Defects and Reproductive Health. Chongqing Population

and Family Planning Science and Technology Research Institute, Chongqing, China.

Keywords: tubal patency; 4D hysterosalpingo-contrast sonography; intrauterine

pressure.

Abstract. We aimed to explore the clinical value of four-dimensional hys-

terosalpingo-contrast sonography (4D-HyCoSy) assisted by intrauterine pres-

sure measurement for evaluating tubal patency. One hundred and thirty-two

patients diagnosed with tubal factor infertility from February 2018 to February

2021 were selected as subjects. With hysterosalpingography diagnosis results as

the gold standard, 4D-HyCoSy was conducted for all patients, and the status of

the fallopian tubes was classified into patency, occlusion, and partial occlusion.

Based on the function of fallopian tubes, 4D-HyCoSy diagnosis results revealed

that fallopian tubes showed bilateral patency, incomplete patency (including

bilateral partial occlusion, unilateral patency, and unilateral partial occlusion,

unilateral patency and unilateral occlusion), unilateral partial occlusion and

unilateral occlusion, and bilateral occlusion. The cutoff value of peak intra-

uterine pressure was determined using the receiver operating characteristic

curve (ROC), specificity, and the area under the ROC curve (AUC) between

4D-HyCoSy alone and 4D-HyCoSy assisted by intrauterine pressure measure-

ments. There were significant differences in the peak intrauterine pressure

among patients with bilateral patency, incomplete patency, unilateral partial

318 Lin et al.

Investigación Clínica 64(3): 2023

Valor clínico de la histerosalpingo-sonografía 4D por contraste,

asistida por medición de la presión intrauterina, para evaluar

la permeabilidad tubárica.

Invest Clin 2023; 64 (3): 317 – 328

Palabras clave: permeabilidad tubárica; ecografía con contraste de histerosalpingo

en cuatro dimensiones; presión intrauterina.

Resumen. Nuestro objetivo fue explorar el valor clínico de la histerosalpin-

go-sonografía con contraste en cuatro dimensiones (4D-HyCoSy) asistida por

la medición de la presión intrauterina para evaluar la permeabilidad tubárica.

Se seleccionaron como sujetos un total de 132 pacientes diagnosticadas como

infertilidad por factor tubárico desde febrero de 2018 hasta febrero de 2021.

Con los resultados del diagnóstico de histerosalpingografía como estándar de

oro, se realizó 4D-HyCoSy para todas las pacientes y el estado de las trompas

de Falopio se clasificó como permeable, ocluída y parcialmente ocluída. Según

la función de las trompas de Falopio, los resultados del diagnóstico 4D-HyCoSy

revelaron que las trompas de Falopio mostraban permeabilidad bilateral, per-

meabilidad incompleta (incluida oclusión parcial bilateral, permeabilidad uni-

lateral y oclusión parcial unilateral, permeabilidad unilateral y oclusión uni-

lateral), oclusión parcial unilateral y oclusión unilateral, y oclusión bilateral.

El valor de corte de la presión intrauterina máxima se determinó utilizando

la curva característica operativa del receptor (ROC), la especificidad y el área

bajo la curva ROC (AUC) entre 4D-HyCoSy sola y 4D-HyCoSy asistida por la

medición de la presión intrauterina. Hubo diferencias significativas en la pre-

sión intrauterina máxima entre pacientes con permeabilidad bilateral, permea-

bilidad incompleta, oclusión parcial unilateral y oclusión unilateral y oclusión

bilateral (p<0,05). Los valores de corte correspondientes de la presión intra-

uterina máxima fueron 24,42, 36,34 y 47,68 kPa, y los valores de AUC fueron

0,812, 0,836 y 0,827, respectivamente. El modelo FSM mostró que el AUC

de 4D-HyCoSy asistida por la presión intrauterina máxima fue de 0,85, con

una sensibilidad más alta (88,13%) que la de 4D-HyCoSy (p<0,05). 4D-HyCoSy

asistido por la medición de la presión intrauterina tiene un valor diagnóstico

significativo en la evaluación de la permeabilidad tubárica.

Received: 24-06-2022 Accepted: 14-01-2023

occlusion, and unilateral and bilateral occlusions (p<0.05). The corresponding

cutoff values of peak intrauterine pressure were 24.42, 36.34, and 47.68 kPa;

AUC values were 0.812, 0.836, and 0.827, respectively. The FSM model showed

that the AUC of 4D-HyCoSy alone, assisted by peak intrauterine pressure was

0.85, with a higher sensitivity (88.13%) than that of 4D-HyCoSy (p<0.05). 4D-

HyCoSy, assisted by intrauterine pressure measurement, has an excellent value

for evaluating tubal patency.

Evaluation of tubal patency 319

Vol. 64(3): 317 - 328, 2023

INTRODUCTION

Infertility is a health concern worldwi-

de. Among the total cases of female infertili-

ty, 54.7% of patients suffer from tubal factor

infertility, and the cases show a year-by-year

uptrend due to increased reproductive in-

fections, sexually transmitted diseases, and

endometriosis

1-3

. Therefore, effective diag-

nostic measures are essential for accurately

evaluating the tubal patency of patients.

Transvaginal hysterosalpingo-contrast so-

nography (TV HyCoSy) is a primary nonin-

vasive method to assess the tubal patency

of infertile patients. As technologies cons-

tantly progress, four-dimensional HyCoSy

(4D-HyCoSy) has been widely applied in

clinical diagnosis. Patients can still under-

go missed diagnosis by this method despite

of its advantages such as simple operation,

low cost, and low risk

4-8

. In recent years, in-

trauterine pressure measurement is a new

auxiliary means to examine fallopian tube

pressure. It can be applied in combination

with 4D-HyCoSy to examine the intrauterine

pressure at a constant speed, improving the

accuracy of the clinical diagnosis and ensu-

ring the safety of patients

9,10

. In this study,

the clinical data of 132 patients with tubal

infertility were analyzed, and the diagnostic

value of 4D-HyCoSy assisted by intrauterine

pressure measurement was assessed for tu-

bal patency.

PATIENTS AND METHODS

General data

One hundred and thirty-two outpatient

infertile patients treated in our hospital’s De-

partment of Obstetrics and Gynecology from

February 2018 to February 2021 were selec-

ted. They were 23-42 years old (28.69±4.32)

and examined at 3-7 d after menstruation,

including 42 primary and 90 secondary in-

fertile patients. This study was approved by

the Ethics Committee of our hospital and

performed following the Declaration of Hel-

sinki. All the patients included in this study

and their families were informed of this stu-

dy and signed an informed consent.

Inclusion criteria

1) Patients with no pregnancy for more

than one year, 2) those whose husbands had

a normal reproductive function, and those

who had sexual harmony with their husband

and took no contraceptive measures, 3) tho-

se with indications confirmed by HyCoSy, 4)

those suspected of primary or secondary tu-

bal infertility, 5) those with negative hystero-

salpingography (HSG) results, and 6) those

whose family members signed the informed

consent after communication.

Exclusion criteria

1) Patients with serious gynecological

diseases (vaginitis, pelvic inflammatory di-

sease, adnexitis, etc.), 2) those complicated

with malignant tumors, 3) those with ovu-

lation failure caused by congenital malfor-

mations or other genetic factors, 4) those

with heart, liver or kidney dysfunction, 5)

those who were pregnant or suspected of

pregnancy, 6) those who suffered from abor-

tion within six months, 7) those who were

allergic to contrast media, or 8) those with

hysteromyoma >5 cm.

Diagnosis methods

HSG is a safe method with high accu-

racy for checking tubal patency. This study

applied HSG diagnosis results as the gold

standard and compared them to 4D-HyCoSy

diagnosis results, and statistical analysis was

carried out.

Apparatus and reagents

In this study, a Philips EPIQ5 color

Doppler ultrasound diagnostic machine

(Philips, Netherlands) was adopted for 4D-

HyCoSy with a probe frequency of 5-9 MHz

under low image quality; the volume angle

of 100-120°, the volume frame angle of 179°,

direction (Up/Down), the frame frequency

of 0.6 and low threshold (20, adjusted accor-

ding to different images). The contrast agent

320 Lin et al.

Investigación Clínica 64(3): 2023

used was SonoVue (59 mg/tube, NMPN:

J20080052, Bracco, Italy). The antispasmo-

dic and anti-inflammatory agents [gentami-

cin (80,000 units) + dexamethasone (2.5

mg) + atropine (0.25 mg) + lidocaine (50

mg)] were added into 20 mL of 0.9% normal

saline, and mixed evenly to prepare a suspen-

sion. Later, 59 mg SonoVue was added into

5 mL of injectable normal saline and mixed

evenly to form a microbubble suspension,

which was diluted with 5 mL of normal saline

before injection.

4D-HyCoSy diagnosis

1) Thirty min before diagnosis, atro-

pine was injected. 2) Upon bladder filling,

the patients were placed in the bladder

lithotomy position. Then the shape of the

patient’s uterus and ovary, relative cross-

section position, and pelvic cavity effusion

were observed. Next, the injection pressure

for bilateral ovaries was slightly increased,

and the ovarian activity was evaluated. 3)

Perineum and vagina were disinfected using

complex iodine; a double-cavity Foley cathe-

ter was placed into the uterine cavity under

the guidance of the abdominal probe, and

1.5-2 mL of normal saline was injected into

the balloon using a syringe. 4) After the size

and position of the balloon were adjusted,

5 mL of normal saline was slowly injected

through the Foley catheter and then pum-

ped back. After that, the tubal patency was

preliminarily evaluated according to the re-

sistance and the amount of liquid pumped

back. 5) The probe was continuously adjus-

ted to turn on the four-dimensional mode,

and the contrast agent was injected slowly.

Next, the solvent data were recorded in real-

time following the optimization of the sam-

pling frame, and the data of liquid pumped

back were recorded. Afterward, the speed

and pressure of the injection were adjusted

at any time based on patients’ adverse reac-

tions. 6) The Foley catheter was removed,

and the uterine cavity was observed under

the radiography mode.

HSG diagnosis

The patients were placed in the supi-

ne bladder lithotomy position, and the first

slice was taken. A vaginal speculum was put

after disinfection. Then the cervical side wall

was fixed with cervical forceps, the second

slice was taken after contrast agent iohexol

was slowly added, and the shape of the ute-

rus was observed. Subsequently, the angle

was adjusted for photography of the third

slice, after which the development of fallo-

pian tubes and uteri were observed. If the

development effect was unsatisfactory, the

medicine could be increased appropriately.

HSG diagnostic criteria were displa-

yed below: 1) Patency: the fallopian tubes

on both sides were completely developed,

showing a natural shape. The contrast agent

overflew normally at the umbrella end and

diffused in the pelvic cavity. There was al-

most no contrast agent left in the fallopian

tubes. 2) Partial occlusion: fallopian tubes

had poor morphology, and a small amount

of contrast agent was left. 3) Occlusion: the

contrast agent gathered in the occlusion

site and did not enter the pelvic cavity.

Combined diagnosis

The receiver operating characteristic

(ROC) curve was plotted to calculate the

cutoff value of intrauterine pressure measu-

rement, and the sensitivity, specificity, and

area under ROC curve (AUC) of 4D-HyCoSy

and combined diagnosis were determined

based on 4D-HyCoSy diagnosis results, which

coincided with the peak intrauterine pressu-

re interval, with HSG diagnosis results as the

gold standard.

Diagnostic criteria of 4D-HyCoSy

1) Patency: there was no resistance

when the contrast agent was injected, the fa-

llopian tubes ran smoothly and softly, and a

large amount of contrast agent overflew from

the umbrella end and diffused in the pelvic

cavity. 2) Partial occlusion: there was positi-

ve resistance during the injection of contrast

Evaluation of tubal patency 321

Vol. 64(3): 317 - 328, 2023

agent, fallopian tubes were stiff and twisted,

the thickness of the lumen was uneven, and

a small amount of contrast agent overflew

from the umbrella end. 3) Occlusion: during

the injection of the contrast agent, there

was significant resistance, no development

in the whole or distal end of fallopian tubes,

and no diffusion of the contrast agent in the

pelvic cavity.

Observation of adverse reactions

Adverse reactions included adverse

drug reactions, which were determined ac-

cording to SonoVue instructions, and ad-

verse non-drug reactions, such as pain, pale

complexion, dizziness, profuse sweating,

hypotension, arrhythmia, nausea, vomiting,

and fainting.

Statistical analysis

The IBM® SPSS23.0 software was uti-

lized for statistical analysis. Measurement

data were expressed as mean ± standard

deviation (

sx ±

) and compared between

groups using the t-test. Numerical data were

expressed as percentages (%) and compared

between groups via the c

test. Dichotomous

logistic regression analysis was conducted

to analyze diagnostic factors, and the finite

state machine (FSM) diagnostic model was

established and verified using the ROC cur-

ve. p<0.05 represented a statistically signi-

ficant difference.

RESULTS

Detection results of tubal patency by

4D-HyCoSy

All 132 patients completed the 4D-

HyCoSy examination, and their images were

clear. Among 264 fallopian tubes, 145 were

open, 42 were occluded entirely, and 77 were

partially occluded. Among them, there were

• 53 cases of bilateral patency (106 fa-

llopian tubes),

• 13 cases of bilateral occlusion (26 fa-

llopian tubes),

• 20 cases of bilateral partial occlusion

(40 fallopian tubes),

• Nine cases of unilateral patency and

unilateral occlusion (9/9 fallopian tu-

bes),

• 30 cases of unilateral patency and

unilateral partial occlusion (30/30 fa-

llopian tubes), and

• Seven cases of unilateral occlusion

and unilateral partial occlusion (7/7 fa-

llopian tubes).

Besides, there were nine cases of arcua-

te uterus, five incomplete mediastinal ute-

rus cases, three intrauterine adhesions, and

two intrauterine polyps (Fig. 1).

4D-HyCoSy and HSG diagnosis results

Within two weeks after the 4D-HyCoSy

diagnosis, 132 patients underwent HSG diag-

nosis. The results showed that among 264

fallopian tubes, 132 were open, 55 were oc-

cluded entirely, and 77 were partially occlu-

ded. In the 4D-HyCoSy diagnosis, the paten-

cy of 212 fallopian tubes conformed to the

HSG examination results, with a diagnostic

coincidence rate of 86.18% (212/264). With

HSG diagnosis results as the gold standard,

the diagnostic coincidence rate of tubal pa-

tency was the highest [84.83% (123/145)],

and that of tubal occlusion and partial oc-

clusion was 80.95% (34/42) and 76.62%

(59/77), respectively (Table 1).

Bilateral patency was defined as open

fallopian tubes on both sides. Incomplete pa-

tency included partially occluded fallopian

tubes on both sides, an open fallopian tube

on one side, a partially occluded fallopian

tube on the other, an open fallopian tube,

and an occluded fallopian tube on the other.

Unilateral partial occlusion and unilateral

occlusion referred to a partially occluded

fallopian tube on one side and an occluded

fallopian tube on the other side. Bilateral

occlusion was defined as occluded fallopian

tubes on both sides. The diagnostic coinci-

dence rate of the 4D-HyCoSy diagnosis in

322 Lin et al.

Investigación Clínica 64(3): 2023

132 patients was 87.12% (115/132), with

HSG diagnosis results as the gold standard

(Table 2).

Intrauterine pressure measurement

results

Seventy out of 132 patients underwent

intrauterine pressure measurement

through the connection with a pressure

measurement device before the 4D-HyCoSy

diagnosis, and their intrauterine pressure

results were obtained. Pairwise compari-

sons of the pressure values were carried out

in six groups. The results revealed no signi-

ficant differences in the peak intrauterine

pressure among patients in the unilateral

patency and the unilateral occlusion group,

unilateral patency and unilateral partial

occlusion group, and the bilateral partial

occlusion group (p<0.05). The patients

Fig. 1. Fallopian tube images obtained after 4D-HyCoSy diagnosis. A. Bilateral patency, B. Bilateral occlusion,

C. Bilateral partial occlusion, D. Unilateral partial occlusion, and unilateral occlusion. E. Unilateral

patency and unilateral partial occlusion, and F. Unilateral patency and unilateral occlusion.

Table 1

4D-HyCoSy diagnosis results

4D-HyCoSy

HSG

Patency Partial occlusion Occlusion Total

Patency 123 (84.83%) 12 (8.28%) 10 (6.90%) 145 (58.94%)

Partial occlusion 7 (9.09%) 59 (76.62%) 11 (14.29%) 77 (31.30%)

Occlusion 2 (4.76%) 6 (1.43%) 34 (80.95%) 42 (17.07%)

Total 132 (53.66%) 77 (31.30%) 55 (22.36%) 264 (100%)

4D-HyCoSy diagnostic

coincidence rate

123/132 (93.18%) 59/77 (76.62%) 34/55 (61.82%) 212/264 (80.30%)

Values n= 132 are expressed in n (%).

Evaluation of tubal patency 323

Vol. 64(3): 317 - 328, 2023

in these three groups were included in the

incomplete patency group (Group A), and

the differences between the bilateral pa-

tency group (Group B), bilateral occlusion

group (Group C), unilateral occlusion, and

unilateral occlusion group (Group D) and

the other groups were significant (p<0.05).

Besides, severer occlusion had higher intra-

uterine pressure (Table 3).

The ROC curve of the peak intrauterine

pressure was plotted. The cutoff value bet-

ween Group B and Group A was 25.42 kPa,

with a sensitivity of 81% and a specificity of

85%. AUC was 0.812 (Fig. 2). The cutoff value

between Group A and Group D was 36.34 kPa,

with a sensitivity of 73% and a specificity of

89%; AUC was 0.836 (Fig. 3). Moreover, the

cutoff value between Group D and Group C

was 47.68 kPa, with a sensitivity of 79% and

a specificity of 87%; AUC was 0.827 (Fig. 4).

Establishment of the combined diagnosis

model

Dichotomous logistic regression analy-

sis was conducted for the 4D-HyCoSy diag-

nosis (A) and intrauterine pressure measu-

rement (B), to evaluate the efficacy of the

combined diagnosis. The results demons-

trated t a significant difference between the

two diagnosis methods (p<0.05), so both

could be used as predictive diagnostic indi-

cators. According to the regression coeffi-

cient of the two variables, the mathematical

diagnosis model of FSM was established as

follows: FSM =1.083 ln(A) + 1.275 ln(B) -

8.23 (Table 4).

Model validation results

The diagnostic efficiency of the FSM

diagnostic model was assessed using the

ROC curve. It was discovered that the com-

bined diagnosis model had a high diag-

nostic value, with an AUC of 0.85. When

FSM=11.3, the model had a high sensitivity

(89.36%), which meant that only three of

70 patients undergoing combined diagno-

sis were misdiagnosed due to a FSM<11.3.

When the FSM=13.8, the model had a high

specificity (92.55%). Besides, the model was

still particularly valuable in the diagnosis of

other patients. The diagnostic efficiency was

compared between the 4D-HyCoSy diagnosis

and the combined diagnosis. The ROC curve

illustrated that the diagnostic value of the

4D-HyCoSy diagnosis was lower than that of

the combined diagnosis. With the maximum

value of the Youden index (YI) as a thres-

hold, the AUC of 4D-HyCoSy diagnosis was

Table 2

Diagnostic results of 4D-HyCoSy [n=132, n (%)]

4D-HyCoSy

HSG

Bilateral

patency

Partial

occlusion

Unilateral partial

occlusion and

unilateral occlusion

Bilateral

occlusion

Total

Bilateral patency 43 (89.58%) 3 (5.00%) 0 (0.00%) 0 (0.00%) 46 (34.85%)

Partial occlusion 5 (1.04%) 50 (84.75%) 0 (0.00%) 1 (6.67%) 60 (45.45%)

Unilateral partial occlusion

Unilateral occlusion

0 (0.00%)

7 (11.86%)

3 (33.33%)

3 (20.00%)

13 (9.85%)

Bilateral occlusion

0 (0.00%) 0 (0.00%) 6 (66.67%) 11 (73.33%) 17 (12.88%)

Total

48 (40.15%) 60 (45.45%) 9 (6.82%) 15 (11.36%) 132 (100%)

4D-HyCoSy diagnostic

coincidence rate

48 (90.57%)

50 (84.75%)

6 (66.67%)

11 (73.33%)

115 (87.12%)

324 Lin et al.

Investigación Clínica 64(3): 2023

0.82, with a sensitivity of 78.04%, which was

markedly lower than that of the combined

diagnosis (sensitivity: 70.13%). However,

the specificity displayed no significant diffe-

rence between the two diagnosis methods

(p>0.05) (Fig. 5). Comparative evalua-

tion indicators for diagnostic efficiency are

shown in Table 5.

Adverse reactions

Among the 132 patients, the majority

had pain during the examination, and the

minority suffered from dizziness and nausea

without adverse reactions such as arrhyth-

mia, vomiting, hypotension, and fainting.

Patients’ adverse reactions were all within

the tolerable range, and no allergic reac-

tions or vaginal bleeding occurred. In addi-

tion, 41 cases (31.06%) had grade 0 adver-

se reactions, 65 cases (49.24%) had grade

I adverse reactions, 19 cases (14.39%) had

grade II adverse reactions, and seven ca-

ses (5.30%) had grade III adverse reactions

(Fig. 6).

Table 3

Intrauterine pressure measurement results.

Group Radiography results n (number of

fallopian tubes)

Pressure

(kPa)

Peak intrauterine

pressure (kPa)

Comparison

group

A Unilateral patency and

unilateral occlusion

5 (10) 17.9~42.6 36.42±3.15 B, C, D <0.05

A Unilateral patency and

unilateral partial occlusion

11 (22) 15.2~34.8 25.47±2.51 B, C, D <0.05

Bilateral partial occlusion 6 (12) 17.2~37.6 32.17±2.74 B, C, D <0.05

Bilateral patency 35 (70) 13.2~28.4 19.43±1.68 A, C, D <0.001

Bilateral occlusion 6 (12) 42.0~63.2 54.35±2.30 A, B, D <0.001

D Unilateral partial occlusion

and unilateral occlusion

7 (14) 25.7~52.3 43.42±1.70 A, B, C <0.05

Fig. 2. ROC curves of Group B and Group C. Fig. 3. ROC curves of Group A and Group D.

Evaluation of tubal patency 325

Vol. 64(3): 317 - 328, 2023

DISCUSSION

Infertility is a common disease in fe-

males, severely damaging patients’ lives and

mental health. It has now become a preva-

lent disease needing treatment in the me-

dical field. Tubal patency makes the propor-

tion of infertile females exceed 50%, so it is a

critical basis for treating infertility to explo-

re efficient methods for diagnosing fallopian

tubes at a general degree, contributing to

early diagnosis and early treatment

Fig. 4. ROC curves of Group D and Group C.

Table 4

Results of dichotomous logistic regression analysis.

Indicator

Regression

coefficient

Standard

error

Wald

value

Odds ratio

(OR)

95%CI p

4D-HyCoSy 1.083 0.531 4.16 2.953 1.009~12.937 0.017

Peak intrauterine pressure 1.275 0.414 9.485 3.579 1.105~13.564 0.015

Fig. 5. ROC curves of combined diagnosis and 4D-

HyCoSy diagnosis.

Table 5

Evaluation results of combined diagnosis and 4D-HyCoSy diagnosis efficiency.

Indicator AUC (95% CI) YI

Threshold

value

Sen

(%)

Spe

(%)

Positive

predictive value

Negative

predictive value

4D-HyCoSy diagnosis 0.82(0.78-0.88) 0.43 69.57 78.04% 70.13% 78.27% 80.36% 53.14%

Combined diagnosis 0.85(0.81-0.92) 0.56 20.93 88.13% 79.46% 87.97% 94.64% 69.23%

In clinical practice, diagnosis methods

commonly used for tubal patency include hy-

drotubation under the ascites (laparoscopic

chromopertubation (LC)), uterine hydrotu-

bation, HSG, hysterolaparoscopy, contrast-

enhanced ultrasonography of fallopian tubes

and X-ray HSG. Among them, traditional hy-

drotubation is a blind operation with a low

diagnostic accuracy rate. Laparoscopy is an

operation causing trauma, which is harmful

to patients. LC diagnosis requires general

326 Lin et al.

Investigación Clínica 64(3): 2023

anesthesia, after which patients have a risk

of massive hemorrhage. HSG exhibits high

accuracy, but some patients are allergic to

iodine. Moreover, X-ray HSG is radioactive to

some extent, and also it cannot be applied

in patients allergic to iodine

12,13

. Hence, a

simple diagnostic method that is easy to

operate with low risk and low cost becomes

a hot spot in the medical field

14-16

. HyCoSy

diagnostic technology is increasingly recog-

nized by doctors and patients since it is safe

and non-invasive, with high accuracy, high

operability, and good repeatability. The 4D-

HyCoSy is a new type of contrast-enhanced

ultrasound technology following 2D and

3D, during which the entire fallopian tubes

can be visually displayed through imaging,

and some fallopian tubes with unique posi-

tions or those in twisted and complicated

shapes can also be well displayed. Through

4D-HyCoSy diagnosis, there remain cases of

missed diagnosis though it is simple and effi-

cient, so there is a necessity to find suitable

auxiliary means to improve the accuracy of

diagnosis.

In 2016, Kong checked the tubal pa-

tency using 4D-HyCoSy assisted by hydro-

gen peroxide, and its diagnostic coinciden-

ce rate (91.8%) was much higher than that

of 4D-HyCoSy alone. Nevertheless, during

4D-HyCoSy diagnosis, scanning in a large

fan-shaped angle can display the occlusion

position of fallopian tubes and the varia-

tions of shape, and the injection pressure

can be appropriately increased according

to the occlusion of fallopian tubes for dred-

ging the slightly adhesive fallopian tubes.

Therefore, determining pressure using the

traditional hand-pushing method is greatly

affected by subjective factors, so a more

intuitive auxiliary means is needed for eva-

luation. In the present study, 132 patients

with tubal factor infertility were selected,

and the tubal patency was detected by 4D-

HyCoSy. Through comparison, it was found

that the patency of 212 fallopian tubes con-

formed to HSG diagnosis results (gold stan-

dard), with a diagnostic coincidence rate

of 86.18%. Besides, the fractional analysis

based on the function of fallopian tubes re-

vealed that the diagnostic coincidence rate

of 4D-HyCoSy was 87.12%. Besides, the in-

trauterine pressure measurement demons-

trated that the pressure was lower when the

fallopian tubes were open, and the more se-

vere the occlusion, the higher the pressure.

Subsequently, the cutoff value in each

group was determined using the ROC curve.

It was discovered that the cutoff value among

bilateral patency, incomplete patency, unila-

teral partial occlusion, unilateral occlusion,

and bilateral occlusion was 25.42 kPa, 36.34

kPa, and 47.86 kPa, respectively, and the AUC

was 0.812, 0.836 and 0.827 respectively. The-

refore, intrauterine pressure measurement

can be applied as an effective means to assist

the 4D-HyCoSy diagnosis to improve the ac-

curacy of diagnosis. Furthermore, to investi-

gate the clinical value of 4D-HyCoSy assisted

by intrauterine pressure measurement in the

evaluation of tubal patency, dichotomous lo-

gistic regression analysis was conducted for

diagnosis factors, and the FSM diagnostic

Fig. 6. Adverse reactions of patients.

Evaluation of tubal patency 327

Vol. 64(3): 317 - 328, 2023

model was established, which was verified by

the ROC curve. The results showed that the

AUC of combined diagnosis was 0.85, with

a higher sensitivity (88.13%) than that of

4D-HyCoSy alone (p<0.05) and a specificity

(79.46%) showing no significant difference

in comparison with that of 4D-HyCoSy alo-

ne, confirming the extremely high diagnostic

value of 4D-HyCoSy assisted by intrauterine

pressure measurement in the evaluation of

tubal patency.

In summary, 4D-HyCoSy, assisted by in-

trauterine pressure measurement, has high

diagnostic value in evaluating tubal paten-

cy. Regardless, this study had a small sample

size so the results may be biased. In the futu-

re, we will conduct multicenter studies with

larger sample sizes to validate our findings.

Conflict of interest

The authors declare that they have no

competing interests.

Funding

This study was financially supported by

2019 Medical Science Research Project of

Hebei Province (No. 20191778).

ORCID numbers

• Chunhong Lin: 0000-0002-1576-6936

• Jianyong Chen: 0000-0001-8207-5433

• Xianguo Li: 0000-0002-2116-8692

• Linlin Wang: 0000-0002-3098-3226

• Fengqin Yan: 0000-0002-3505-5429

• Ye Chang: 0000-0003-2062-469X

• Xueniu Yang: 0000-0002-4370-2104

Authors contribution

The first two authors contributed equa-

lly to this study.

REFERENCES

1. Liang N, Wu QQ, Li JH, Gao FY, Sun FL,

Guo CX. Causes of misdiagnosis in asses

sing tubal patency by transvaginal real-

time three-dimensional hysterosalpingo-

contrast sonography. Rev Assoc Med Bras

2019; 65(8): 1055-1060. https://doi.

org/10.1590/1806-9282.65.8.1055.

2. Ruan SM, Zheng Q, Wang Z, Hu HT, Chen

LD, Guo HL, Xie XY, Lu MD, Li W, Wang

W. Comparison of real-time two-dimen

sional and three-dimensional contrast-en-

hanced ultrasound to quantify flow in an

in vitro model: a feasibility study. Med Sci

Monit 2019; 25: 10029-10035. https://doi.

org/10.12659/MSM.919160.

3. Carson SA, Kallen AN. Diagnosis and ma

nagement of infertility: a review. JAMA

2021; 326(1): 65-76. https://doi.org/

10.1001/jama.2021.4788 .

4. Ludwin I, Ludwin A, Nastri CO, Coelho

Neto MA, Kottner J, Martins WP. Inter-ra

ter reliability of air/saline HyCoSy, HyFoSy

and HyFoSy combined with power doppler

for screening tubal patency. Ultraschall

Med 2019; 40(1): 47-54. https://doi.org/

10.1055/s-0043-120111.

5. Chen F, Quan J, Huang P, You X. Hys

terosalpingo-contrast sonography with

four-dimensional technique for screening

fallopian tubal patency: let’s make an ex

ploration. J Minim Invasive Gynecol 2017;

24(3): 407-414. https://doi.org/10.1016/j.

jmig.2016.12.011.

6. Gu P, Yang X, Zhao X, Xu D. The value of

transvaginal 4-dimensional hysterosalpin

go-contrast sonography in predicting the

necessity of assisted reproductive techno

logy for women with tubal factor infertili-

ty. Quant Imaging Med Surg 2021; 11(8):

3698-3714. https://doi.org/10.21037/

qims-20-1193.

7. Aggarwal D. Can HyCoSy replace laparos

copy and hysteroscopy as a method to assess

tubal patency and uterine cavity lesions.

IOSR-JDMS 2019; 18(5): 80-83. https://

doi.org/10.9790/0853-1805098083.

328 Lin et al.

Investigación Clínica 64(3): 2023

8. Ojha K, Goel T, Vinayagam D. Evaluation

of Tubal Patency (HyCoSy, Doppler). In Ul

trasound Imaging in Reproductive Medici-

ne 2019 (pp. 239-248). Springer, Cham.

9. Gao YB, Yan JH, Yang YD, Sun J, Dong JY,

Cui GH. Diagnostic value of transvaginal

four‑dimensional hysterosalpingo‑con

trast sonography combined with recana-

lization in patients with tubal infertility.

Niger J Clin Pract 2019; 22(1): 46-50.

10. Shi J, Li S, Wu H, He Y, Yi W, Xu J, Liu

H, Guan Y. The influencing factors of ve

nous intravasation during transvaginal

four-dimensional hysterosalpingo-contrast

sonography with SonoVue. Ultrasound Med

Biol 2019; 45(9): 2273-2280. https://doi.

org/10.1016/j.ultrasmedbio.2019.05.003.

11. Exalto N, Emanuel MH. Clinical as

pects of HyFoSy as tubal patency test

in subfertility workup. Biomed Res

Int 2019; 2019: 4827376. https://doi.

org/10.1155/2019/4827376.

12. Wallyn J, Anton N, Mertz D, Begin-Colin

S, Perton F, Serra CA, Franconi F, Lemai

re L, Chiper M, Libouban H, Messaddeq

N, Anton H, Vandamme TF. Magnetite-

and iodine-containing nanoemulsion as a

dual modal contrast agent for X-ray/mag

netic resonance imaging. ACS Appl Mater

Interfaces 2019; 11(1): 403-416. https://

doi.org/10.1021/acsami.8b19517.

13. Zhang J, Zhang X, Bian J, Wang C. Com

paration of magnetic resonance hysterosal-

pingography and hysterosalpingosonogra-

phy for the assessment of fallopian tubal

occlusion of female infertility: A protocol

for systematic review and meta-analysis.

Medicine 2022; 101(3): e28532. https://

doi.org/10.1097/MD.0000000000028532.

14. Gad MS, Dawood RM, Antar MS, Ali SE.

Role of hysteroscopy and laparoscopy in eva

luation of unexplained infertility. Menoufia

Med J 2019; 32(4): 1401-1405. https://

doi.org/10.4103/mmj.mmj_387_18.

15. Dishuck CF, Perchik JD, Porter KK, Gunn

DD. Advanced imaging in female infertili

ty. Curr Urol Rep 2019; 20: 77. https://doi.

org/10.1007/s11934-019-0942-0.

16. Lo Monte G, Capobianco G, Piva I, Caser

ta D, Dessole S, Marci R. Hysterosalpingo

contrast sonography (HyCoSy): let’s make

the point! Arch Gynecol Obstet 2015;

291(1): 19-30. https://doi.org/10.1007/

s00404-014-3465-4.