Current challenges in the diagnosis and management of ectopic pregnancies

The current issue of the European Journal of Ultrasound includes a number of articles discussing various types of ectopic pregnancies. Ectopic pregnancies develop partially or completely outside the uterine cavity, and due to the fetal growth in an abnormal anatomical location, these pregnancies are potentially associated with hemorrhagic morbidity [1].

Helmy-Bader and Koch provide a comprehensive overview of the various types of ectopic pregnancy in their CME article entitled “Ultrasound assessment and management of different forms of ectopic pregnancy”. Images and video clips are used to explain the diagnosis and current classification of ectopic pregnancies, and the corresponding management options are presented [2].

The introduction of transvaginal ultrasound, particularly in connection with the measurement of human chorionic gonadotropin levels, greatly improved the diagnosis of ectopic pregnancies beginning in the late 1980 s. Prior to this, ectopic pregnancies were often only able to be diagnosed by means of invasive procedures like laparoscopy or during emergency procedures to treat acute intraabdominal bleeding. The use of transvaginal ultrasound resulted in a significant reduction in morbidity and mortality among affected women by allowing early diagnosis and treatment [3] [4]. Consequently, the most common type, tubal pregnancy, has changed from a primary surgical emergency to a condition that can be diagnosed early and often treated with medication.

The better visualization also resulted in the detection of other rare types of ectopic pregnancy. Although they are rare, their timely diagnosis is still essential [5] [6] [7] [8] [9] [10].

Based on the ESHRE recommendations, ectopic pregnancies can be classified as extrauterine, like tubal pregnancies, and intrauterine, like intramural, cervical, and interstitial pregnancies [11].

The cesarean scar ectopic pregnancy (CSEP) represents a special type, and its classification as an ectopic pregnancy is controversial among experts [12]. One reason for this is that a CSEP can at least theoretically be carried to term – in contrast to other ectopic pregnancies, even though this is associated with extremely high maternal and neonatal mortality and morbidity [2].

The cover story of this issue by Jost et al. describes 2 cases with the rare combination of a CSEP and an intact intrauterine pregnancy, which is referred to as a heterotopic cesarean scar pregnancy, and provides insight into possible management options. An article by Cai et al. discusses the sonographic features, clinical management, and pregnancy outcome of the even rarer heterotopic intramural pregnancy based on a case series [13].

Although CSEP is rare with an estimated incidence of approximately 1:2000, it is becoming increasingly clinically relevant, due to the global increase in C-section rates resulting in an increase in the number of patients at risk [14] [15]. As described in the CME article by Helmy-Bader and Koch in this issue of the journal, the corresponding guidelines and recommendations recommend early intervention rather than a conservative approach [16] [17] [18] [19]. A number of management approaches for CSEP in the first trimester ranging from surgical interventions and local procedures under ultrasound guidance to systemic therapies are described [20] [21].

According to a current study based on the international CSEP registry, which is the most comprehensive collection of data on this topic to date, suction evacuation is one of the most commonly used surgical treatment methods, and systemic methotrexate (MTX) is one of the most commonly used medication-based treatment methods [21]. Based on this registry data, 14 % of all CSEP patients and 52 % of those not treated surgically received first-line systemic MTX [21]. Systemic MTX has been used off-label since the 1980 s, with a dose of 1 mg/kg bodyweight or 50 mg/m² body surface area being administered [20] [22] [23]. Although the effectiveness of this treatment in CSEP patients has been questioned in literature, systemic MTX remains widely used, which can presumably be attributed to the ease of use and broad availability [24].

A current study at the Department of Gynecological Ultrasound and Prenatal Diagnostics at the Women’s Clinic of the University Hospital Basel examined whether a subgroup of patients that could benefit from systemic MTX treatment could be identified. 72 patients with confirmed CSEP in the first trimester and primary first-line systemic MTX were included in the CSEP registry and compared with respect to various clinical and sonographic patient characteristics.

Additional treatment was required in 65.3 % of the patients, with suction evacuation (30 %) and surgical excision (26 %) being primarily performed, followed by combined local and systemic medication-based treatments (21 %), evacuation in combination with uterine artery embolization (9 %), hysterectomy (6 %), second-line systemic methotrexate (4 %), uterine artery embolization (2 %), and other methods (2 %).

The characteristics examined and the corresponding ultrasound findings are provided in [Table 1]. A significant difference (p < 0.05) between patients treated successfully with MTX and those requiring additional second-line treatment was seen with respect to the following parameters: Crown-rump length (CRL) (p = 0.004), peak β-hCG levels (p = 0.005), and fetal cardiac activity at the time of diagnosis (p = 0.021). A small CRL, a low peak β-hCG level, and a lack of cardiac activity were associated with a higher probability of systemic MTX treatment success ([Table 1]). The success rate of systemic MTX (48.6 % [17/35]) was significantly higher in the case of a lack of fetal cardiac activity than in the case of confirmed cardiac activity (18.8 % [6/32]). Further ROC analyses showed an area under the curve of 0.643 for CRL as the sole predictor. For all 3 predictors combined, a slightly higher AUC of 0.716 was seen ([Fig. 1]).

Table 1

Characteristics	Successful treatment (n = 25)	Unsuccessful treatment (n = 47)	p-value	n
Maternal age (y)	34 (28–47)	36 (26–49)	0.542	72
Parity	2 (1–4)	2 (1–4)	0.865	72
No. of prior C-sections	1.8 ± 1.1	1.8 ± 0.8	0.8126	72
CSEP type I	9 (36.0 %)	14 (31.1 %)	0.879	70
CSEP type II	16 (64.0 %)	31 (68.9 %)	0.879	70
Gestational age (w)	6 (4–13)	6 (5–12)	0.679	70
CRL (mm)	4 (0–10)	8 (0–44)	0.004*	44
GS (mm)	14 (6–51)	20.5 (3–57)	0.126	57
Peak β-hCG (IU/L)	6,703 (528–68,312)	22,348 (22–100,000)	0.005*	66
Fetal heartbeat present	6 (26.1 %)	26 (59.1 %)	0.021*	67
β-hCG resolution time (d)	52.5 (21–128)	57.5 (6–185)	0.780	52
Placenta lacunae	4 (26.7 %)	7 (29.2 %)	1.000	39
Placenta location			0.550	32
Anterior previa	8 (100 %)	20 (83.3 %)
Posterior previa	0 (0.00 %)	4 (16.7 %)
Degree of vascularization			0.549	63
Normal	10 (43.5 %)	13 (32.5 %)
Increased	13 (56.5 %)	27 (67.5 %)
RMT (mm)	3.00 (0.0–8.1)	1.50 (0.0–5.2)	0.127	60
AMT (mm)	12.8 (5.0–16.8)	12.5 (4.1–23.1)	0.656	26

Data presented as median (min.–max.) or number (percentage). *Significant p-value < 0.05. CSEP: cesarean scar ectopic pregnancy; GS: gestational sac; CRL: crown-rump length; hCG: human chorionic gonadotropin. RMT: residual myometrial thickness; AMT: adjacent myometrial thickness.

Fig. 1 ROC curve for prediction of successful treatment based on CRL alone and on combined predictors (CRL, presence of fetal heartbeat, and peak β-hCG). AUC: area under the curve; CRL: crown-rump length; FHB: fetal heartbeat; PeakbHCG: peak β-human chorionic gonadotropin.

These results show that systemic MTX therapy alone is not sufficient in most CSEP cases. In agreement with these results, other studies on CSEP and ectopic pregnancies also indicated that the β-hCG level, the size of the embryo, and the presence of a fetal heartbeat could be predictive factors for the success of treatment with systemic MTX [22] [25] [26] [27]. The published success rates for systemic MTX are between 56 % and 86 %. However, a direct comparison of the study results is only possible on a limited basis since the definitions of treatment failure vary [26] [28].

Based on these results and the availability of effective alternative treatment methods, single first-line systemic MTX should not be used to treat CSEP [19].

Elena Brunnschweiler

Prof. Dr. med. Gwendolin Manegold-Brauer

Prof. Dr. med. Philipp Klaritsch

Conflict of Interest

The authors declare that they have no conflict of interest.

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Publication History

Article published online:
09 February 2026