Diagnostic efficacy of virtual organ computer-assisted analysis in measuring the volume ratio of subchorionic hematoma with serum progesterone

Abstract

BACKGROUND

Subchorionic hematoma (SCH) is a common complication in early pregnancy characterized by the accumulation of blood between the uterine wall and the chorionic membrane. SCH can lead to adverse pregnancy outcomes such as miscarriage, preterm birth, and other complications. Early detection and accurate assessment of SCH are crucial for appropriate management and improved pregnancy outcomes.

AIM

To evaluate the diagnostic efficacy of virtual organ computer-assisted analysis (VOCAL) in measuring the volume ratio of SCH to gestational sac (GS) combined with serum progesterone on early pregnancy outcomes in patients with SCH.

METHODS

A total of 153 patients with SCH in their first-trimester pregnancies between 6 and 11 wk were enrolled. All patients were followed up until a gestational age of 20 wk. The parameters of transvaginal two-dimensional ultrasound, including the circumference of SCH (Cs), surface area of SCH (Ss), circumference of GS (Cg), and surface area of GS (Sg), and the parameters of VOCAL with transvaginal three-dimensional ultrasound, including the three-dimensional volume of SCH (3DVs) and GS (3DVg), were recorded. The size of the SCH and its ratio to the GS size (Cs/Cg, Ss/Sg, 3DVs/3DVg) were recorded and compared.

RESULTS

Compared with those in the normal pregnancy group, the adverse pregnancy group had higher Cs/Cg, Ss/Sg, and 3DVs/3DVg ratios (P < 0.05). When 3DVs/3DVg was 0.220, the highest predictive performance predicted adverse pregnancy outcomes, resulting in an AUC of 0.767, and the sensitivity, specificity were 70.2%, 75% respectively. VOCAL measuring 3DVs/3DVg combined with serum progesterone gave a diagnostic AUC of 0.824 for early pregnancy outcome in SCH patients, with a high sensitivity of 82.1% and a specificity of 72.1%, which showed a significant difference between AUC.

CONCLUSION

VOCAL-measured 3DVs/3DVg effectively quantifies the severity of SCH, while combined serum progesterone better predicts adverse pregnancy outcomes.

Key Words: Subchorionic hematoma; Virtual organ computer-assisted analysis; Gestational sac; Serum progesterone; Ultrasound parameters; Adverse pregnancy outcomes

Core Tip: This study demonstrates the utility of virtual organ computer-assisted analysis (VOCAL) in assessing subchorionic hematoma (SCH) severity by measuring the 3D volume ratio of SCH to gestational sac (GS) in early pregnancy. The combination of VOCAL measurements with serum progesterone levels significantly improves the prediction of adverse pregnancy outcomes. Higher ratios of SCH to GS size were associated with adverse outcomes, with VOCAL-measured 3DVs/3DVg showing the highest predictive performance. These findings highlight the importance of advanced imaging techniques and biomarkers for early SCH assessment and management in pregnant patients.

INTRODUCTION

A subchorionic hematoma (SCH) is separated between the chorionic plate and floor decidua and appears in a crescent sono-anechoic area. SCH is the most common abnormal ultrasound finding in the first trimester and is accompanied by vaginal bleeding and abdominal pain. SCH is often observed in pregnant women with threatened abortions at 9–20 wk of pregnancy[1]. In previously published studies, the incidence of SCH in early pregnancy was approximately 0.46% and 39.5%, depending on the study population, SCH size, and gestational age at diagnosis[2,3].

However, the effect of SCH on pregnancy outcomes remains unclear. Due to the complex etiology of SCH, different causes, SCH sizes, and even different parts of the SCH have a great impact on pregnancy outcomes. More studies have confirmed that SCH size is an important indicator of the severity of hematoma and an important factor in determining pregnancy outcomes[4-8].

Mantoni et al[9] suggested using the first ultrasound examination to evaluate the effect of hematoma size on pregnancy outcome. The methods to evaluate the hematoma size are divided into subjective and semi-quantitative. The subjective method is based on the experience of sonographers, while the semi-quantitative method is divided into the “SCH wrapping gestational sac (GS) ratio method” according to the ratio of SCH and GS size measured using ultrasound,[1,10] the “SCH/GS area ratio method,”[10,11] and the SCH/GS volume ratio method[2,12]. However, most SCH forms are irregular and the measurement results differ among physicians. Obtaining the SCH area and volume using the calculation formula for a cut plane and regular image is inaccurate, which makes the conclusions of different studies different[13].

Virtual organ computer-aided analysis (VOCAL) is a method to reconstruct the shape of tissues and organs and automatically and accurately measure the volume, which can avoid the measurement error of two-dimensional (2D) ultrasound to a certain extent. VOCAL technology has been applied to volumetric measurements of various organs and tissues, such as in obstetrics, to evaluate fetal brain structure[14,15], fetal heart[16], gestational sac[17], hematoma[18,19], and placental volumes[20]. However, few studies have evaluated the volume of SCH and early pregnancy outcomes using VOCAL technology, and progesterone can reflect fetal growth and abortion. Therefore, this study analyzed the measurement of SCH volume and progesterone using the VOCAL technique and explored the diagnostic efficacy of SCH and GS volume ratio alone and in combination with serum progesterone on early pregnancy outcomes by calculating the SCH to GS volume ratio.

MATERIALS AND METHODS

Clinical data

This study was conducted at the Second Affiliated Hospital of Soochow University between January 2020 and May 2023. The study population consisted of 153 pregnant women in their early trimesters who were diagnosed with SCH using ultrasound. Their ages ranged from 21 to 39. All patients underwent transvaginal first 2D and three-dimensional (3D) ultrasound examinations at 6–11 wk of gestation. The normal pregnancy group underwent ultrasound examination at 20 wk of gestation and showed the fetal heart rate or medical records of the fetal term delivery. In the adverse pregnancy group, patients showed no fetal heart rate or abortion on ultrasound examination before 20 weeks of gestation; therefore, early pregnancy results were classified as adverse pregnancy. The study was approved by the Medical Ethics Committee of the Second Affiliated Hospital of Soochow University, and all patients provided informed consent verbally.

Ultrasound measurement

Transvaginal two-dimensional ultrasound multi-angle scan by a Voluson E8 or S10 machine (GE Healthcare, Milwaukee, United States) equipped with a multifrequential endocavitary volumetric probe (RIC5-9-D).After multiangle scanning and showing the maximum section of the SCH, the circumference of the maximum section of the SCH (Cs) and surface area (Ss) were traced. The circumference of GS (Cg) and surface area (Sg) were measured and calculated in the same manner. The Cs/Cg and Vs/Vg ratios were calculated separately.

Three-dimensional ultrasonography also was performed by GE Volusion E8 or S10 ultrasound diagnostic instrument, equipped with the VOCAL measurement software package (GE Healthcare, Milwaukee, United States), the probe scan angle was set at 120. The 3-DUS imaging system was turned on for automatic image acquisition after obtaining the maximum section of the SCH. Open the VOCAL measurement software, use 30° rotation compensation, get six levels, the software automatically calculates the SCH 3 D ultrasound volume (3DVs). The sample box size was adjusted, including the entire GS, to obtain a GS 3D ultrasound volume (3DVg), and 3DVs/3DVg was calculated (Figure 1). The above examinations were completed by two physicians who had worked for more than 10 years. For cases with inconsistent SCH measurements, the third senior expert reviewed and judged the final result and took the final result as the final statistical result.

Figure 1 Transvaginal three-dimensional ultrasound showed three-dimensional volume of gestational sac, three-dimensional volume of subchorionic hematoma, and this patient showed fetal arrest at 18 wk. A: Three-dimensional volume of gestational sac was 42.84 cm³; B: Three-dimensional volume of subchorionic hematoma was 3.79 cm³.

Measurement of serum levels of progesterone

Serum test: Five milliliters of fasting cubital venous blood were collected, centrifuged at 3000 rpm for 5 min, stored in a cryogenic environment, and serum progesterone levels were detected using chemiluminescence analysis.

Statistical analysis

Using R4.0 statistical software, t-test was used for comparison between measurement data, median for non-normal distribution, χ² test for qualitative data. Through the ROC curve, the diagnostic threshold, sensitivity and other indexes were calculated. The difference between 3DVs/3DVg alone and AUC of early adverse pregnancy outcomes were compared by Z test. A paired χ² test compared the sensitivity of 3DVs/3DVg by VOCAL on the diagnosis of early adverse pregnancy outcomes. Statistical significance was observed at P <0.05.

RESULTS

General data comparison

Of the 153 patients with SCH, 57 belonged to the adverse pregnancy group and 96 to the normal pregnancy group. Patients in the adverse pregnancy group (42.1%) experienced more vaginal bleeding than those in the normal pregnancy group (17.7%) (P < 0.05). No statistically significant difference was observed between the adverse pregnancy and normal pregnancy groups in terms of age, labor rate, presence of abdominal pain, uterine fibroids, pregestational diabetes, and chronic hypertension (P > 0.05) (Table 1).

Table 1 Comparison of the demographic data between the two groups, n (%).

	Adverse pregnancy group (n = 57)	Normal pregnancy group (n = 96)	P value
Age	29.4 (4.2)	28.9 (3.5)	0.424
Parity			0.390
Primipara	31 (53.8)	58 (60.4)
Multipara	26 (46.2)	38 (39.6)
Vaginal bleeding			0.028
Yes	24 (42.1)	17 (17.7)
No	33 (57.9)	79 (82.3)
Abdominal pain			0.891
Yes	33 (57.9)	58 (60.4)
No	24 (42.1)	38 (39.6)
Hysteromyoma			1.000
Yes	3 (5.3)	4 (4.2)
No	54 (94.7)	92 (95.8)
Diabetes before pregnancy			0.713
Yes	2 (3.5)	4 (4.2)
No	55 (96.5)	92 (95.8)
Chronic hypertension			1.000
Yes	2 (3.5)	3 (3.1)
No	55 (96.5)	93 (96.9)

The comparison of SCH and GS sizes between the two groups

The adverse pregnancy group SCH Cs, Ss, and 3DVs were 4.6 (3.1, 6) cm; 2.1 (1.5, 3) cm²; and 2.9 (2.2, 3.5) cm³; the normal pregnancy group SCH Cs, Ss, and 3DVs were 3.2 (2.1, 4.2) cm; 1.3 (0.8, 1.9) cm²; and 1.5 (0.6, 2.4) cm³, and the difference between groups was statistically significant (P < 0.05).

The adverse pregnancy groups Ss/Sg, Vs/Vs, and 3DVs/3DVg were 0.5 (0.4, 0.6); 0.3 (0.2, 0.5); and 0.3 (0.2, 0.5), which were higher than those in the normal pregnancy group, and the difference between groups was statistically significant (P < 0.05) (Table 2).

Table 2 Comparison of ultrasound parameters between patients in the adverse and normal pregnancy groups.

	Adverse pregnancy group (n = 57)	Normal pregnancy group (n = 96)	P value
SCH
Cs (cm)	4.6 (3.1, 6)	3.2 (2.1, 4.2)	< 0.001
Ss (cm2)	2.1 (1.5, 3)	1.3 (0.8, 1.9)	< 0.001
3DVs (cm3)	2.9 (2.2, 3.5)	1.5 (0.6, 2.4)	< 0.001
GS
Cg (cm)	9 (7.2, 10.5)	9.2 (7.9, 11.6)	0.214
Sg (cm2)	6.6 (3.6, 9.9)	7.1 (4.4, 10.7)	0.411
3DVg (cm3)	8.4 (5.3, 15.6)	12.6 (6.4, 21.3)	0.057
SCH/GS
Cs/Cg	0.5 (0.4, 0.6)	0.3 (0.2, 0.4)	< 0.001
Ss/Sg	0.3 (0.2, 0.5)	0.2 (0.1, 0.3)	< 0.001
3DVs/3DVg	0.3 (0.2, 0.5)	0.1 (0.1, 0.2)	< 0.001

SCH: Subchorionic hematoma; Cs: The circumference of SCH, Ss: The surface area of SCH; Cg: The circumference of GS; Sg: The surface area of GS; 3DVs: The three-dimensional volume of SCH; 3DVg: The three-dimensional volume of GS.

The ROC curve showed that 2.180 cm³ was the best cut-off for the three DVs, with an AUC of 0.743. The 3DVs/3DVg had the highest value with the best cut-off of 0.220, producing an AUC of 0.767. The sensitivity, specificity, positive predictive value, and negative predictive value were 70.2%, 75%, 62.5%, and 80.9% respectively (Table 3).

Table 3 Differential diagnostic efficacy of different subchorionic hematoma sizes for adverse versus normal pregnancy.

	ROC	Cut-off	Sensibility	Specificity	Positive predictive value	Negative predictive value
Cs (cm)	0.671 (0.579, 0.763)	4.340	0.561	0.760	0.582	0.745
Ss (cm2)	0.697 (0.611, 0.784)	1.350	0.825	0.510	0.500	0.830
3DVs (cm3)	0.743 (0.661, 0.826)	2.180	0.807	0.719	0.630	0.863
Cs/Cg	0.262 (0.180, 0.344)	0.400	0.737	0.677	0.575	0.713
Ss/Sg	0.710 (0.624, 0.797)	0.360	0.474	0.885	0.711	0.739
3DVs/3DVg	0.767 (0.691, 0.844)	0.220	0.702	0.750	0.625	0.809

SCH: Subchorionic hematoma; Cs: The circumference of SCH; Ss: The surface area of SCH; Cg: The circumference of GS; Sg: The surface area of GS; 3DVs: The three-dimensional volume of SCH (3DVs); 3DVg: Three-dimensional volume of GS; ROC: Receiver operating characteristic.

3DVs/3DVg combined with progesterone for the diagnosis of early adverse pregnancy

The AUC, sensitivity, specificity, and positive and negative predictive values of 3DVs/3DVg combined with progesterone for early adverse pregnancy were 0.824 (95%CI: 0.756, 0.891), 77%, 82.1%, 88.1%, and 67.6%, respectively (Table 4). Comparison of diagnostic efficacy after 3DVs/3DVg alone and combined progesterone showed significant AUC (Z = -2.211, P = 0.027), specificity (χ² = 18.69, P = 0.000), sensitivity (χ² = 28.93, P = 0.000), and 3DVs/3DVg combined with progesterone improved the diagnostic efficacy of early adverse pregnancy.

Table 4 3DVs/3DVg and progesterone for early adverse pregnancy.

	ROC	Cut-off	Sensibility	Specificity	Positive predictive value	Negative predictive value
3DVs/3DVg	0.767 (0.691, 0.844)	0.220	0.702	0.750	0.625	0.809
Progesterone	0.649 (0.557, 0.741)	18.2	0.677	0.625	0.756	0.530
3DVs/3DVg combined progesterone	0.824 (0.756, 0.891)	0.664	0.770	0.821	0.881	0.676

3DVs: Three-dimensional volume of subchorionic hematoma; 3DVg: Three-dimensional volume of GS; ROC: Receiver operating characteristic.

DISCUSSION

SCH is a common disease in obstetrics and is the main imaging method used to evaluate the occurrence of SCH in pregnant women during early pregnancy; it is the basis for the clinical diagnosis of SCH. However, due to the irregular morphology of most SCH and the subjective nature of the measurement among ultrasound physicians, the measurement results differ between different physicians, with varying research conclusions[5,21,22]. Therefore, more objective and accurate imaging methods are needed to quantify SCH size and study the effect of SCH on pregnancy outcomes. The evaluation of SCH size, measured only in a single plane, or calculating the volume using an ellipsoid formula, cannot accurately evaluate SCH with an irregular shape, while the reconstruction and measurement of SCH volume with VOCAL technology, which is less affected by morphological irregular factors, can more accurately and reliably react to SCH volume[18,19]. This study introduced the following three parameters: Ss/Sg, Vs/Vg, and 3DVs/3DVg, and the results showed that the greater the ratio of the three, the greater the risk of adverse pregnancy. That is, the larger the SCH, the smaller the GS, and the higher the adverse pregnancy rate, which is consistent with previous studies[4,23]. The optimal cut-off for 3DVs/3DVg was 0.220, yielding an AUC of 0.767, and the sensitivity, specificity, and positive and negative predictive values were 70.2%, 75%, 62.5%, and 80.9%, respectively. This suggests that 3DVs/3DVg have a high diagnostic value for early adverse pregnancy outcomes. Sauerbrei et al[24] confirmed that the volume ratio method can predict the pregnancy outcome of patients better than the simple area and perimeter ratio methods[21,22]. Sauerbrei et al[24] suggest that as SCH increases, it expands to the bottom decidual invasion, leads to excessive proteolytic enzyme release, damages decidual vessels, the early pregnancy placenta villus is not mature, and the uterine decidua is not strong, causing SCH to increase easily, further aggravating the chorion plate and bottom decidual separation, and larger SCH can make 30%-40% of the placenta from the endometrium, thus further compressing the pregnancy sac, causing a high incidence of spontaneous abortion in the first trimester of pregnancy[21,24,25].

The factors associated with abortion in pregnant women with threatened abortion are more complex, and abnormal embryonic development and genetic, immune, and endocrine abnormalities can lead to abortion in pregnant women[26,27]. Simple imaging and clinical indications are often used to predict maternal pregnancy outcomes; however, their specificities are relatively low[28]. Studies have shown that progesterone is an important indicator for determining whether pregnancy continues in patients with threatened abortions. Bioactive progesterone secreted by the ovary can maintain the intracellular ion concentration and uterine smooth muscle cell membrane permeability and can promote the normal growth and development of embryos by inhibiting smooth muscle excitability[29]. The progesterone test results in this study showed that the adverse pregnancy group had higher progesterone levels than that in the normal pregnancy group. The AUC was 0.649, 67.7%, 62.5%; the positive predictive value was 75.6%; and the negative predictive value was 53%. The AUC of adverse pregnancies after 3 DVs/3DVg and progesterone administration significantly increased to 0.824 (P = 0.027).

Therefore, 3DVs/3DVg combined with progesterone may improve the diagnostic efficacy of early pregnancy outcomes in patients with SCH. Additionally, the sensitivity, specificity, positive predictive value, and negative predictive value of the combined adverse pregnancy outcomes were 77%, 82.1%, 88.1%, and 67.6%, respectively, indicating that 3DVs/3DVg combined with progesterone more accurately evaluated early pregnancy outcomes in patients with SCH and guided effective clinical intervention to improve maternal pregnancy outcomes and fertility quality.

At present, how to accurately predict the outcome of pregnancy has become the focus of obstetrics, this study will combine three-dimensional ultrasound and progesterone level in the diagnosis of threatened abortion early pregnancy outcome, the results show higher sensitivity and specificity, can monitor threatened abortion pregnant women 3DVs/3DVg and progesterone level, guide clinical treatment plan, early active and effective intervention, improve pregnancy outcomes.

This study has certain limitations. First, the sample size was small and should be further expanded in future studies. Second, this study combined only progesterone levels. In the future, other laboratory indicators, such as placental growth hormone and human chorionic gonadotropin, and ultrasound indicators, such as the uterine artery and cervical length, can be developed to evaluate and predict pregnancy outcomes.

CONCLUSION

In conclusion, reconstruction and measurement of SCH volume using the VOCAL technique allow for a relatively accurate assessment of SCH volume in patients with first-trimester pregnancy. Combining the 3DVs/3DVg with progesterone could further improve the predictive value of adverse pregnancy outcomes.