Keywords ultrasound - free fluid - urgency - laparoscopy - ectopic pregnancy
Introduction
In the last two decades, substantial progress has been made in the diagnosis of ectopic
pregnancy (ECP) by transvaginal sonography (TVS), leading to direct ECP visualization
in the vast majority of cases [1 ]
[2 ]
[3 ]
[4 ]
[5 ]
[6 ]. In contrast, urgency remains debatable since the clinical course of ECP covers
a large spectrum with different prognoses. It varies from spontaneous resolution as
described in 42% of cases [7 ], including cases without [8 ] or only limited free fluid (FF) on TVS [9 ], justifying expectant [7 ]
[10 ] or conservative [11 ] management, to a potentially life-threatening condition, indicating emergency intervention
without delay [12 ].
Usually, the danger arising from ECP is defined by severe conditions such as abdominal
pain, acute abdomen, low or decreasing venous hemoglobin levels (HB), and hemodynamic
instability [13 ]
[14 ]
[15 ]
[16 ]
[17 ]. All these conditions are mostly related to occult intra-abdominal blood loss diagnosed
as FF on TVS and confirmed as free blood (FB) in laparoscopy (LSC), appearing as hemoperitoneum
with liquid and clotted parts [6 ].
Any assessment of FB is more or less imprecise [18 ] even if based on intraoperative blood aspiration [12 ]. However, in cases with a suspicion of ECP, the amount of FF on TVS was found to
correlate with FB in LSC, paving the way to comprehensively define preoperative urgency.
An estimate of FB 300–400 mL has been proposed as a preoperative cutoff value to diagnose
severe hemorrhage, declaring high urgency as well as the need for rapid operative
intervention [5 ]
[12 ]
[19 ]
[20 ].
In this study, we investigated the value of FF assessment on TVS and other potentially
predictive factors to define not only high but also low urgency.
Methods
This study is a retrospective cohort analysis on prospectively collected cases between
January 2012 and March 2020 of laparoscopically investigated ECP. Only cases with
adequate documentation of FF on TVS and FB in LSC were included ([Fig. 1 ]).
Fig. 1 Flowchart showing the 482 patients with diagnosed ectopic pregnancy (ECP) on transvaginal
sonography (TVS), advised to undergo operative confirmation and treatment by laparoscopy
(LSC), who were eligible for this study.
We extracted demographics, risk factors, clinical and laboratory findings, TVS examinations,
and findings in laparoscopy from the patient’s digital chart file ([Table 1 ]). All laboratory measures including the exact time of each blood examination were assessed (compare
[Table 1 ]): The last HB before operation, the first HB after operation, the difference between
them, and the last β-HCG before operation.
Table 1 Characteristics of study cohort.
Characteristics
Value
Data are given as n (%), mean ± SD, median (IQR). * Only the last measurement before
the operation was considered. ** Including two conversions to laparotomy. ART: artificial
reproduction therapy; CUA: congenital uterine anomaly; ECP: ectopic pregnancy; FB:
free blood; FF: free fluid; HB: venous hemoglobin concentration; β-HCG: β-human chorionic
gonadotropin; IUD: intrauterine contraceptive device; LSC: laparoscopy.
Patients, n
343
Anamnesis
Age, y (mean ± SD (range))
33.4 ± 5.6 (20.4–46.3)
Duration of pregnancy after LMP, w + d (mean ± SD (range))
6+3 ± 1+3 (2+0–10+4)
No birth (0-para), n (%)
204 (59)
Only vaginal birth (one or more), n (%)
72 (21)
Only c-section (one or more), n (%)
60 (17)
Vaginal birth and c-section (one or more each), n (%)
6 (2)
No notification, n (%)
1
Risk factors (multiple choice possible), n (%)
None
141 (41)
Previous ECP
61 (18)
Abdominal operations (excluding c-section)
48 (14)
Infertility treatment
44 (13)
Smoking
48 (14)
Infections
22 (6)
Endometriosis
26 (8)
ART (current pregnancy)
21 (6)
IUD in situ
10 (3)
After sterilization
7 (2)
Tubal pathology
3 (1)
Clinical symptoms, n (%)
None
41 (12)
Only vaginal bleeding
54 (16)
Only pain
93 (27)
Pain and vaginal bleeding, hemodynamically stable
146 (43)
Hemodynamically unstable
9 (3)
Laboratory findings
β-HCG (IU/L) pre-operation (n = 340), median (IQR)*
1978 (657–4638)
<1500 (IU/L), n (%)
144 (42)
<100 (IU/L), n (%)
13 (4)
<20 (IU/L), n (%)
6 (2)
<1 (IU/L), n (%)
2 (1)
Hb preoperative (g/L) (n=338), mean ± SD (range)*
125.9 ± 13.7 (39–154)
Hb postoperative (g/L) (n=189), mean ± SD (range)
102.9 ± 20.1 (41–140)
Hb difference (g/L) (n=188), mean ± SD (range)
–19.4 ± 14.4 (–59–33)
Treatment
Laparoscopy, n (%)**
343 (100)
Number of preoperative consultations, n (mean ± SD (range)) (n = 342)
2.2 ± 1.0 (1–6)
Duration of in-house stay, d (mean ± SD (range)) (n = 329)
1.9 ± 1.1 (1–8)
The sonographic examination was typically performed in a supine position on a gynecologic chair with a slightly
elevated upper body. This examination was usually done by a resident on duty and supervised
by a staff physician. FF includes different types of blood consistency with liquid
and clotted parts. In case of ECP, we counted any representation of FF found in the
pelvic or abdominal cavity as part of FB, independently from its echogenicity [6 ]
[19 ]
[20 ]
[21 ]
[22 ]. Following the concept of the sentinel clot, which appears first in the vicinity
of the bleeding source [23 ]
[24 ], we primarily relied on TVS ([Fig. 2 ]), and, if needed, extended the examination by transabdominal sonography (TAS) to
assess the entire abdomen, especially Morison’s pouch (hepatorenal, right upper abdomen)
and Koller’s pouch (lienorenal, left upper abdomen).
Fig. 2 Appearance of severe hemoperitoneum on transvaginal sonography (TVS) and laparoscopy
(LSC), defined as ≥ 300 ml intra-abdominal free blood (FB). 1a TVS diagnosis: severe liquid and mild clotted free fluid (FF), 700 ml, 1b LSC confirmation: moderate liquid and severe clotted FB, total 600 ml. 2a TVS: severe liquid and mild clotted FF, 1500 ml, 2b LSC: severe liquid and moderate clotted FB, 1000 ml. 3a TVS: moderate liquid and severe clotted FF, 1500 ml, 3b LSC: severe liquid and severe clotted FB, 3000 ml, spurting arterial bleeding. 4a TVS: severe clotted FF, 700 ml, 4b LSC: severe clotted and moderate liquid FB, 1000 ml.
FF (TVS) was not described in detail in the clinical routine, so that three experienced
sonographers reviewed the complete dataset. The experts rated each case regarding
the total amount of FF in milliliters, as well as separately for liquids and clots,
and assigned them to one of the four semiquantitative categories ([Table 2 ]): no FF, minimal FF (only in pouch of Douglas (POD), less than 3 × 3 cm), moderate
FF (only in the POD more than 3 × 3 cm), severe FF (in the POD more than 3 × 3 cm
and/or adnex and/or excavatio vesicouterina and/or Morison's pouch), trapped fluid
outside the ovary (e.g., hematosalpinx) or inside the ovary (e.g., corpus luteum graviditatis)
was not counted as FF [6 ]. In cases of divergent estimates, the reviewers tried to achieve consent through
discussion. Otherwise, the opinion of the majority (2 to 1) was recorded.
Table 2 Liquids and clots. Liquid and clotted free fluid (FF) on transvaginal sonography (TVS)
and liquid and clotted free blood (FB) in laparoscopy (LSC) were correlated using
Spearman’s rank correlation. Free fluid “not defined” was excluded from the calculation.
Data are given as n (%). Definitions of semiquantitative groups of liquid and clotted FF (TVS) : no FF, mild FF (only in the pouch of Douglas (POD), less than 3×3 cm); moderate
FF (only in the POD, more than 3×3 cm, but not exceeding uterine fundus); severe FF
(in POD, exceeding the uterine fundus). Definitions of quantitative groups for liquid and clotted FB (LSC) : no FB (0 ml); mild FB (1–99 ml), moderate FB (100–299 ml), severe FB (≥ 300 ml)
based on inspection and estimation, not necessarily by aspiration and quantification.
Liquid free blood (LSC)
No
Mild
Moderate
Severe
Total
P
Liquid free fluid (TVS)
n (%)
n (%)
n (%)
n (%)
n (%)
No
45 (50)
40 (34)
5 (9)
6 (8)
96 29)
<0.001
Mild
26 (29)
61 (52)
31 (54)
10 (14)
128 (38)
Moderate
8 (9)
10 (9)
12 (21)
13 (18)
43 (13)
Severe
11 (12)
6 (5)
9 (16)
43 (60)
69 (21)
Total
90 (100)
117 (100)
57 (100)
72 (100)
336 (100)
Clotted free blood (LSC)
No
Mild
Moderate
Severe
Total
P
Clotted free fluid (TVS)
n (%)
n (%)
n (%)
n (%)
n (%)
No
98 (63)
26 (44)
12 (26)
4 (6)
140 (42)
<0.001
Mild
41 (26)
23 (39)
14 (30)
9 (13)
87 (27)
Moderate
16 (10)
9 (15)
17 (36)
16 (23)
58 (18)
Severe
1 (1)
1 (2)
4(9)
41 (59)
46 (14)
Total
159 (100)
59 (100)
44 (100)
70 (100)
331 (100)
The beginning of LSC was assessed by its protocolled start time. We defined the complete
intraperitoneal FB as being equal to hemoperitoneum, and equal to the total amount of FB, clotted, and
liquid together ([Fig. 2 ]). FB was estimated by the operator regularly at the beginning of the operation,
not necessarily being measured by aspiration. Only in cases of low or very low quantities,
where numeric estimations were not given, we transformed the verbal descriptions as
follows: “no” to 0 mL, “minimal” to 10 mL, “few” to 30 mL, “some” to 50 mL, thereby
consciously assigning these descriptions to the group of FB < 100 mL. Similar to FF,
we divided FB into four categories ([Table 2 ]) and assessed it separately for liquid and clots. We set the stop of bleeding equal
to the beginning of the operation. Furthermore, the presence or absence of ECP rupture
was recorded.
We investigated the value of FF assessment on TVS as well as other potentially predictive
factors for defining not only high (FB ≥ 300 mL) but also low urgency (FB < 100 mL) ([Fig. 2 ], image 2a).
Data were collected in Microsoft Excel (Excel 2019, Microsoft Corporation, Redmond,
Washington, USA). Statistical analyses were performed using R version 4.0.0 (R Foundation
for Statistical Computing, Vienna, Austria). Continuous variables are presented as
median with interquartile range (IQR) or mean ± standard deviation (SD) with range.
Continuous and ordinal variables were correlated using Spearman’s rank correlation
rho. Changes in continuous and ordinal variables from TVS to LSC were analyzed using
Wilcoxon's signed rank test with continuity correction. Differences between groups
were assessed using the Wilcoxon rank sum test with continuity correction and the
Kruskal-Wallis test. Categorical and ordinal variables are presented as frequencies
and percentages. Differences in categorical variables between groups were assessed
using Pearson’s chi-square test and Fisher’s exact test as appropriate. Proportions
like sensitivity, specificity, positive and negative predictive value are presented
with 95% Wilson confidence intervals (CI). Two-sided p-values less or equal to 0.05
were considered statistically significant. Univariate and multivariable linear regressions
were performed to predict FB. Variables with skew distributions were logarithmically
transformed for these analyses. For transformations, zero values of FF and FB were
set to 10 mL. Variables were included based on p-values < 0.2 in univariate analyses
and clinical knowledge. A best subset of variables for prediction of FB was selected
based on the Bayesian information criterion (BIC) using the procedure bestglm. The
best model was used in logistic regressions to predict low and high urgency. The results
are presented as odds ratios (OR) with 95% CI. Predictors of urgency were evaluated
using receiver operator characteristic (ROC) curves and presented as areas under the
curve (AUC) with 95% CI.
Prior to this retrospective study, ethics approval by the local ethics committee was
obtained. Only patients who provided written general consent for the incorporation
of their data into research were included. This study considered the STROBE criteria.
Results
In total, 343 patients with confirmed tubal and nontubal ECP and adequately documented
FF on TVS and FB in LSC were included ([Fig. 1 ]). Demographics are given by [Table 1 ]. Based on the literature and our own experience, we analyzed a selection of potentially
predictive factors to define urgency in ECP (Supplementary Table 1 ).
Time of diagnosis and clinical presentation . In our cohort, the great majority (85%, 293/343) declared symptoms such as pain
and/or vaginal bleeding. No asymptomatic patient (with LMP) presented severe FB ≥
300 mL before 7+0 (weeks + days) ([Table 1 ]). Only one asymptomatic woman (2%, 1/41) had sonographically diagnosed FF and operatively
confirmed FB of 300 mL, but at 7+5 with β-HCG 1,103 IU/L. She had no prior history
of ECP and received infertility treatment. Furthermore, all nine patients with hemodynamic
instability (3%, 9/343) presented severe FB ([Fig. 3 ]). Here, pregnancy was diagnosed in consequence of the emergency examination, and
not before, taking place in two patients at 4+0 or earlier, and in three patients
at 7+0 or later.
Fig. 3 Total amounts of diagnosed free fluid on transvaginal sonography (TVS) in relation
to confirmed free blood in laparoscopy (LSC). Values of free blood are jittered, making
overlapping data points visible. Blue lines mark free fluid and free blood at 100
ml and 300 ml. Black line represents linear regression. Free fluid was only recorded
in 7 of 9 hemodynamically instable patients (red plus signs).
Hemoglobin: Pre- and postoperative HB as well as its difference correlated significantly
with FB (LSC) (all p < 0.001) ([Fig. 4 ], Supplementary Table 1 ).
Fig. 4 Hemoglobin concentration (HB) and total intra-abdominal free blood (FB) in laparoscopy
(LSC). Relation between a HB before the operation, b HB after the operation, c HB difference between them, and the confirmed amount of FB in LSC (equal to hemoperitoneum).
Values of FB are jittered, making overlapping data points visible. Blue lines mark
FB at 100 ml and 300 ml. Red plus signs indicate cases with circulatory instability.
Black line represents linear regression of FB in all cases. Only in one case of hemodynamic
instability (FB was 2500 ml), postoperative HB was measured after the administration
of two RBC, resulting in an HB difference of +26 g/L. Only one patient with FB 50
ml showed a higher Hb difference of +33 g/L which remained unexplained.
Hemoglobin : Pre- and postoperative HB as well as its difference correlated significantly with
FB (LSC) (all p < 0.001) (Supplementary Table 1 ).
Hemodynamic instability . Seven of the patients with hemodynamic instability (78%, 7/9) were diagnosed with
FF 1,657 ± 883 (400–3,000) and confirmed as hemoperitoneum of FB 2,478 ± 924 (500–3,500)
(mL, mean ± SD (range)). Conversion to laparotomy was necessary in two cases. The
preoperative HB (96 ± 26 (39–122)), postoperative HB (60 ± 12 (41–78)), and HB difference (43 ± 10 (28–59) (g/L) correlated significantly with FB. The operators
defined hemoperitoneum as a consequence of slow but long-lasting bleeding (89%, 8/9)
rather than as a result of a sudden rise in bleeding due to arrosion of one or more
bigger vessels (11%, 1/9) ([Fig. 2 ]).
Correlation of FF (TVS) with FB (LSC). We found a strong correlation between the total amounts of FF and FB (Spearman’s rank
correlation p < 0.001, rho = 0.7) (Supplementary Table 1 , [Fig. 3 ]).
Liquid and clotted parts. We found moderate to high correlations between FF on TVS and FB in LSC, for both
liquid (rho 0.47, p < 0.001) and clotted parts (rho 0.60, p < 0.001) ([Fig. 3 ]). No difference was found between the categories of liquid and clotted parts, comparing
FF and FB ([Table 2 ]). Otherwise, the difference between these parts depended significantly on the amount
of FB (p < 0.001, Kruskal-Wallis rank sum test): In higher total amounts of FF, deviations
were greater, both in terms of under- and overestimation ([Fig. 5 ]). However, there was no evidence of a systematic error to under- or overestimate
liquids or clots (p 0.15 and 0.30, Wilcoxon signed rank test with continuity correction).
Fig. 5 Liquids and clots. Deviations of liquid and clotted free fluid (FF) on transvaginal
sonography (TVS) from liquid a and clotted b free blood (FB) in laparoscopy (LSC) are presented as subtraction of the assigned
category number (no FF = 1, mild FF = 2, moderate FF = 3, severe FF = 4, for details
compare Table 2). Negative values (to the left) indicate underestimation, positive
values (to the right) indicate overestimation of liquid a or clotted parts b of FB. The blue lines mark FB at 100 ml and 300 ml.
Major bleeding site. Tubal ECP, representing 91% (311/343) of all confirmed ECP, showed FB of 100 mL (median,
range 0–3,000 mL). The other seven ECP locations together covered 9%, showing very
differing amounts of FB ([Fig. 6 ]). Due to the low numbers in all locations other than tubal ECP, major bleeding site
was not used for risk stratification.
Fig. 6 Ectopic pregnancy (ECP) location and intra-abdominal free blood. Arrangement of groups
according to the median of free blood in comparison to tubal ECP, the strongest group
representing 91% (311/343) of cases. The blue lines mark free blood at 100 ml and
300 ml. Abd: abdominal; cer: cervical; CUA: in congenital uterine anomaly; C-s: in
C-section scar; het: heterotopic; NA: location not available; int: interstitial; ova:
ovarian; tub: tubal.
Risk stratification of intraperitoneal hemorrhage . The following factors correlated significantly with the total amount of FB in LSC
(Supplementary Table 1 ): the absence of clinical symptoms, only vaginal bleeding, only pain, hemodynamic
instability, age, HB pre- and postoperative, HB difference, FF, also in its morphologically
different aspects (FF liquid and clotted), and ruptured ECP. In univariate analysis (Supplementary Table 1 ), most of these factors correlated significantly with the total amount of FB (LSC),
examined also for two different cutoff values (100 mL and 300 mL). We did not process
the clearly not significant parameters (obstetric history), underpowered (hemodynamically
unstable), postoperative (HB postoperative, HB difference, ruptured ECP) as well as
factual dependent parameters (FF clotted and FF liquid). In multivariable linear regression ([Table 3 ]), we analyzed clinical symptoms as a categorical variable with five categories of
symptoms. In this analysis, clinical symptoms, HB preoperative, and FF were significant
predictors of FB. Best subset selection among 32 tested models found FF together with
preoperative HB as the BIC optimal predictor. The second-best model consisted of FF
alone. In the logistic regressions for prediction of low and high urgency, FF was the only independent predictor for
both low and high urgency. Preoperative HB was only significant for high urgency ([Table 3 ]).
Table 3 Multivariate analysis of elaborated independent predictors of intra-abdominal free
blood in laparoscopy (LSC), focused on < 100 ml and ≥ 300 ml. All subsets of the five
variables (clinical symptoms, age, β-HCG, HB preoperative, FF) were compared (2^5
= 32 models).
Free blood (LSC)
MLR*
BIC OLRM**, LR***
< 100 ml
≥300 ml
Parameter
P
OR (95% CI)
P
OR (95% CI)
P
*MLR: multivariable linear regression. **BIC OLRM: Bayesian information criterion
optimal linear regression model.***LR: logistic regression. ∆log10 transformed. “Clinical
symptoms: none” served as the reference for the other clinical symptoms.
Clinical symptoms
<0.001
None
reference
Only vaginal bleeding (n)
0.2
Only pain (n)
0.006
Pain and vaginal bleeding (n), hemodynamically stable
0.023
Hemodynamically unstable (n)
0.001
Age (years)
0.55
β-HCG preoperative (IU/L) ∆
0.79
HB preoperative (g/L)
0.024
1.015 (0.991–1.041)
0.24
0.966 (0.939–0.993)
0.015
FF total (ml) ∆
<0.001
0.102 (0.060–0.168)
<0.001
30.1 (13.0–81.1)
<0.001
ROC analysis revealed FF (TVS) as an excellent discriminatory parameter for defining low urgency
as well as high urgency. Adding preoperative HB to FF revealed only a marginal, probably
clinically not relevant improvement in the prediction of FB in LSC for defining high
urgency ([Fig. 7 ]). The Youden Index based on the calculated ROC curves was used to determine the
best differentiating threshold for low and high urgency. The optimum cutoff value
for predicting low urgency (FB < 100 mL) was 150 mL FF; the optimum cutoff value for
predicting high urgency (FB ≥ 300 mL) was 250 mL FF ([Table 4 ]).
Fig. 7 ROC analysis for the prediction of the total amount of intra-abdominal free blood
(FB) in laparoscopy (LSC) presenting the favorite parameters resulting from multivariate
analysis, separate for a low urgency (FB < 100 ml), and b high urgency (FB ≥ 300 ml). Predictors of urgency were presented as area under the
curve (AUC) with 95% confidence intervals. The black solid line represents free fluid
(FF) on TVS alone. The red dotted line represents the combination of FF (TVS) and
preoperative hemoglobin.
Table 4 Testing different cutoff values of free fluid (FF) on transvaginal sonography (TVS)
to predict intra-abdominal free blood (FB) in laparoscopy (LSC), separately for low
urgency (defined as FB < 100 ml) and high urgency (defined as FB ≥ 300 ml).
Sens.: sensitivity; spec.: specificity; PPV: positive predictive value; NPV: negative
predictive value.
Low urgency
Sens.
Spec.
PPV
NPV
Free fluid (TVS)
(%)
(%)
(%)
(%)
(ml)
(95% CI)
(95% CI)
(95% CI)
(95% CI)
<10
30.9
92.9
80.6
58.5
24.3–38.4
88.1–95.9
69.1–88.6
52.6–64.2
<50
53.1
82.9
74.8
65
(45.4–60.6)
(76.6–87.9)
(66.1–81.8)
(58.4–71.0)
<100
77.2
77.6
76.7
78.1
(70.1–83)
(70.8–83.3)
(69.6–82.5)
(71.3–83.7)
<150
89.5
65.9
71.4
86.8
(83.8–93.3)
(58.5–72.6)
(64.9–77.2)
(79.9–91.6)
<200
92.6
60
68.8
89.5
(87.5–95.7)
(52.5–67.1)
(62.4–74.6)
(82.5–93.9)
<300
96.9
46.5
63.3
94
(93.0–98.7)
(39.1–54)
(57.1–69.1)
(86.8–97.4)
<500
100
28.2
57
100
(97.7–100)
(22.0–35.4)
(51.2–62.7)
(92.6–100)
<1000
100
10.6
51.6
100
(97.7–100)
(6.8–16.1)
(46.1–57.1)
(82.4–100)
High urgency
Sens.
Spec.
PPV
NPV
Free fluid (TVS)
(%)
(%)
(%)
(%)
(ml)
(95% CI)
(95% CI)
(95% CI)
(95% CI)
≥50
94
44.2
35.9
95.7
(86.7–97.4)
(38.1–50.4)
(29.9–42.5)
(90.2–98.1)
≥100
92.8
63.1
45.6
96.3
(85.1–96.6)
(56.9–68.8)
(38.2–53.1)
(92.2–98.3)
≥200
83.1
81.9
60.5
93.6
(73.7–89.7)
(76.7–86.2)
(51.4–69.0)
(89.5–96.1)
≥300
75.9
91.6
75
91.9
(65.7–83.8)
(87.5–94.4)
(64.8–83.0)
(87.9–94.7)
≥500
51.8
98
89.6
85.9
(41.2–62.2)
(95.4–99.1)
(77.8–95.5)
(81.4–89.5)
≥1000
21.7
100
100
79.3
(14.2–31.7)
(98.5–100)
(82.4–100)
(74.5–83.4)
Outcome and survival : All 343 patients recovered from ECP and left the hospital within 8 days.
Discussion
Our study revealed FF on TVS as the main factor for reasonably defining low and high
urgency in ECP.
Time of diagnosis and clinical presentation . None of the asymptomatic patients with LMP (12%, 41/343) presented severe FB (LSC)
before 7+0 (weeks + days). Furthermore, none of the patients with hemodynamic instability
(3%, 9/343) were aware of their pregnancy, since no one had attended regular first
pregnancy examination before 7+1 or had done a urine pregnancy test as usual when
menstruation is lacking.
The correlation of FF (TVS) with FB (LSC) was highly significant, not only for the total amounts ([Fig. 3 ]) but also for liquid and clotted parts separately ([Fig. 5 ], [Table 2 ]). The time-related differences between the assessments in TVS and LSC are considered
to be irrelevant. TVS is well known as a reliable method for assessing FF in the pelvis
[5 ]
[6 ]
[12 ]
[21 ]
[25 ]
[26 ]
[27 ] whereas different semiquantitative approaches have been applied [6 ]
[9 ]
[12 ]
[19 ]
[21 ]. We found the equivalent of a hemoperitoneum of 300 mL in a POD filled with FF of
any echogenicity, and just exceeding the edge of the fundus on TVS ([Fig. 2 ], image 2a). It is an easily reproducible landmark and in perfect agreement with
other assessments [5 ]
[9 ]
[12 ].
Liquid and clotted parts. A blurred uterus contour or a generally remarkably reduced view may serve as strong
indicators for clots in contact with the uterus ([Table 2 ]). For liquid and clotted parts, a higher amount of FB correlated with higher deviations
of TVS-estimated FF ([Fig. 5 ]). Although the occurrence of clots may be considered an indicator for urgency [12 ], we found that liquid and clotted parts on TVS and LSC typically appeared in an
approximately 1:1 relation between 100 mL and 1000 mL, so that differentiation of
liquidity would probably not help to define urgency ([Fig. 5 ]).
Predictors of intraperitoneal hemorrhage. None of the investigated preoperative parameters was able to predict low or high
urgency, except for the assessment of FF on TVS ([Fig. 3 ], Supplementary Table 1 ), and notably HB ([Table 3 ]), but only as a low degree additive for the assessment in high urgency ([Fig. 7 ]). Hemodynamic instability constitutes a common presentation in medically less developed
countries. However, in our cohort, these rare events did not have a relevant influence
on risk stratification. Moreover, stable hemoperitoneum with ECP undergoing spontaneous
resolution may be treated expectantly. Pain was a significant indicator for “not low
urgency” only in univariate analysis. The optimum cutoff value was FF = 150 mL for
predicting low urgency, and FF = 250 mL for high urgency ([Fig. 7 ]). The search for reasonable cutoff values may also be based on > 90% sensitivity
for defining high urgency and > 90% specificity for defining low urgency ([Table 4 ]). This approach would lead to FF < 10 mL determining low urgency and FF ≥ 100 mL
determining high urgency, which is substantially more restrictive than the cutoffs
we had empirically chosen. Prospective clinical studies should determine the meaningful
application of cutoff values for FF assessment in diagnosing FB.
Possible limitations of the study are its retrospective design, the impracticality
of precise free fluid assessment even during laparoscopy, and the lack of reproducibility.
Gestational age is based only on the reported LMP so that we cannot exclude a stronger
influence of this parameter on urgency. In our cohort, 44 women became pregnant following
fertility treatment, whereby the potential confounder of an increased amount of FF
after ovarian stimulation cannot be excluded. Strengths included the high denominator,
the histological ECP diagnosis, and the gold standard outcomes. Future considerations
should include the implementation of this approach in a multicenter study.
We conclude that assessing FF on TVS is of outmost relevance in assigning low and high urgency,
supporting an optimum ECP management. The more FF in TVS, the higher the urgency.
However, the exact cutoff values remain debatable. We found the equivalent of a hemoperitoneum
of 300 mL, defining high urgency, in a POD filled with FF of any echogenicity, and
just exceeding the edge of the fundus on TVS.
