Cesarean scar pregnancy: a ten-year single center experience

doi:10.21203/rs.3.rs-3808967/v1

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Cesarean scar pregnancy: a ten-year single center experience

https://doi.org/10.21203/rs.3.rs-3808967/v1

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Introduction:

Cesarean scar pregnancy (CSP) is a rare but potentially life-threatening form of ectopic pregnancy which incidence has been constantly raising during the last decades. The aim of this study was to describe the epidemiological characteristics of CSP in our population and to investigate the impact of different treatments on the maternal outcomes and prognosis.

Patients and methods:

This was a retrospective study including all patients diagnosed with CSP and who were admitted in our maternity between January 2010 and December 2020. Data were collected from the patients’ medical records. We compared outcomes (hospital stay duration, serum BHCG levels, complications, new pregnancy) in 2 groups: group 1 was treated with systemic injection of methotrexate (MTX) associated with dilatation curettage (DC) and group 2 was managed with uterine artery embolization (UAE) and DC.

Results:

The mean age was 33.5 years old. Most of patients (80%) reported history of 2 or more previous cesarean sections. The mean gestational age at diagnosis was 8 weeks. Patients presented mostly with isolated amenorrhea. The mean βHCG serum level at admission was 52352.4 milliunits/mL. The diagnosis was made on ultrasonographic examination in all cases. The Management of CSP in group 1 was associated with a significantly shorter resolution time of serum βHCG levels (p = 0.006). A shorter hospital stay duration was also reported in group 1 but with no statistical significance (p = 0.31). Complications were more observed in group 2 but with no statistical significance (p = 0.61).

Conclusion:

We concluded that UAE associated with an ultrasound-guided DC might be an interesting option for the management of CSP. An early and appropriate diagnostic with identification of cases at higher risk is necessary to reduce complications.

Cesarean scar

ectopic pregnancy

methotrexate

embolization

Cesarean scar pregnancy (CSP) is a rare but potentially life-threatening form of ectopic pregnancy. First reported in 1978 by Larsen et al. as an ectopic implantation of embryos in a previous uterine scar [1], the estimated incidence of CSP is actually 1:1800 to 1:2226 of all pregnancies [2].

During the last decade, the incidence of CSP has been notably rising, probably due to the steady increase in cesarean section rates as well as the advances in imaging techniques and increased awareness [3, 4].

An early diagnosis and an adequate management of this condition are necessary. In fact, CSP can be associated with increased maternal morbidity and mortality due to uterine rupture, massive hemorrhage, an abnormally invasive placenta, and the need for hysterectomy [2, 5]. The diagnosis is typically made on transvaginal ultrasonography associated with a Doppler scan [6]

Given the small number of CSPs reported in case series and reviews, there is no current consensus algorithm for their optimal management. The 2016 guidelines of the Royal College of Obstetricians and Gynecologists state that there is insufficient evidence to support one treatment option over another [7]. In fact, CSP can be managed either with medically conservative modalities such as in situ or systemic methotrexate injections, or with surgical and interventional methods such as uterine artery embolization, ultrasound guided aspiration, and transvaginal, hysteroscopic, or laparoscopic excision [8]

The aim of this study was to describe the epidemiological characteristics of CSP in our population and to investigate the impact of different treatments on the maternal outcomes and prognosis.

Patients:

This is a monocenter retrospective study. The study was conducted within a period of ten years between January 2010 and December 2020. The medical records of 20 patients diagnosed and managed for CSP were reviewed.

We included in our study all cases of CSP. The diagnosis of CSP was based on:

A history of previous cesarean deliveries (CD).
Positive -HCG levels in the serum
Ultrasound criteria including: an empty uterine cavity and cervix, an absent or thin myometrium separating the gestational sac and/or placenta from the posterior wall of the bladder, a gestational sac and/or placenta located at the level of the previous uterine scar, and rich trophoblastic blood flow on the Doppler examination.

We did not include patients not previously diagnosed with CSP who presented at the emergency room with a complication such as a uterine rupture or uncontrolled hemorrhage.

Patients were divided into two groups according to management strategies:

The first group included patients treated with a systemic intramuscular methotrexate (MTX) injection (1 mg/kg), associated with ultrasound-guided dilatation curettage and/or laparotomy.
The second group underwent UAE in an interventional radiology department. A catheter was inserted into the right femoral artery and extended bilaterally into the uterine arteries. A gelation sponge particle embolic agent was then injected. An angiographic exam was performed later in order to verify the occlusion of the CSP’s nourishing vessels. An ultrasound-guided dilatation curettage was performed within 24 hours after the UAE in an operating room under general or regional anesthesia.
In case of a complication, such as uterine rupture or uncontrolled hemorrhage, a laparotomy was performed, allowing the ectopic pregnancy to be removed and the myometrium defect to be repaired.

Serum βHCG levels were measured four and seven days after the MTX injection. On the first day following UAE and dilatation curettage, serum levels of -HCG were measured. The hospital stay duration and the serum βHCG levels’ resolution time were reported. All patients were followed up 4 months after being discharged and a possible oligomenorrhae or new pregnancy were reported.

Statistical analysis:

Statistical analysis was performed using IBM SPSS 20.0 software package. Descriptive statistics were calculated for all measured variables. Outcome data were presented as percentages (n, %), median and means ± standard deviation (SD).

Both management strategies were compared using the non-parametric Mann-Whitney test or Student test for quantitative variables. Pearson’s test or fisher’s test were used to compare qualitative variables. Statistical significance was set at p < 0.05.

During the study, a total of 1753 cases of ectopic pregnancies were recorded. Among them, 20 patients diagnosed with CSP were included in the study.

The mean age was 33.5 years old ± 4.7. The mean gravidity was 4.5(± 1.6) and the mean parity was 2.9(± 1.5). The mean number of previous cesarean deliveries reported was 2.7(± 1.3). Five subjects (25%) reported undergoing at least one abortion, of which two patients (10%) were treated by dilatation and curettage (DC). The baseline characteristics are reported in Table 1.

Table 1

Baseline characteristics.
Baseline characteristics		N	%
Age (years)	< 35	3	15
	30–34	7	35
	≥ 35	10	50
Social background	Low	1	5
Social background	Medium	19	95
Gestity	≤ 2	2	10
	3–4	8	40
	≥ 5	10	50
Parity	Pauciparous (≤ 4)	16	80
Parity	Multiparous (> 4)	4	20
Previous CD	< 2	4	20
Previous CD	≥ 2	16	80

CSP was diagnosed in twelve cases (60%) during an early ultrasonographic examination for isolated amenorrhea. Six patients (30%) presented with amenorrhea associated with vaginal bleeding, one patient (5%) with isolated vaginal bleeding and one patient (5%) with lower abdominal pain coupled with amenorrhea.

The mean gestational age at diagnosis was 8 weeks (± 2 weeks). At the time of admission, 95 percent of the patients had normal vital signs. One patient (5%), with circulatory collapse, was admitted to the emergency room. Abdominal examination was normal in 95% of the subjects, one patient (5%) had pelvic tenderness at initial abdominal exam. The gynecological examination showed mild vaginal bleeding in six cases (30%).

The mean βHCG serum level at admission was 52352.4 milliunits/mL (5910 milliunits/mL to 151326 milliunits/mL).

The mean hemoglobin levels at admission were 11.8 g/dL (± 1.5 g/dL). Eight patients (40%) had anemia at the initial blood count.

The CSP diagnosis was made in all patients using the ultrasonography criteria stated above (Table 2).

Table 2

Ultrasonographic findings
Ultra sonographic findings		Number (n)	Percentage (%)
Maximum diameter of the GS (mm)	10–19 mm	9	45
	20–29 mm	4	20
	30–39 mm	5	25
	40–50 mm	2	10
Myometrial thickness (mm)	< 3 mm	7	35
	3–4 mm	7	35
	> 4 mm	6	30
Presence of an embryo		10	50
Fœtal heart beat		7	35
Free fluid in the pouch of Douglas		1	5
Type-« on the scar »		13	65
Type « in the niche »		7	35

In terms of management strategies, 40% of patients underwent systemic MTX injection laparotomy, 55% underwent UAE associated with DC, and 5% were managed with systemic MTX associated with UAE and DC.

The main complications reported after treatment were uterine rupture (5%), circulatory collapse (5%) and incomplete uterine rupture (15%). A transfusion was needed in two cases (10%).

The mean duration of hospital stay was 13 days (5–37 days). The mean time for serum β HCG levels’ resolution was 43 days (15–117 days). Half of the patients presented with oligomenorrhea, and no new pregnancies were reported.

Analytical statistics did not show statistical significance between the two groups of study with respect to epidemiological and clinical characteristics. Myometrial thickness on ultrasound examination was more important in group 1 (p = 0.06).

Serum βHCG levels decreased by 4.4% compared to initial levels 7th day after Methotrexate injection versus 42.7% compared to initial levels at day 1 following UAE and DC (p = 0.006). Hospital stay duration was shorter in group 2 but with no statistical significance (p = 0.31). Complications were more frequently observed in group 2 with no significant difference (p = 0.61).

Characteristics and outcomes of both management strategies used in our study are compared in Tables 3 and 4.

Table 3

Comparison of patients’ characteristics
	Group 1	Group 2	p
	Mean(SD)	Mean (SD)	p
Parity	3.4 (1.6)	2.6 (1.3)	0.25*
Number of CD	3.1 (1.4)	2.4 (1.2)	0.23*
Prior abortion by	0.13 (0.3)	0.33 (0.6)	0.47*
Gestational age (weeks)	6.7 (1.3)	8.5 (2.1)	0.05*
Serum β HCG levels (mUI/ml)	47015.7 (48438.5)	55910.2 (48604.4)	0.28
GS (mm)	20.7 (12.4)	26.5 (10.4)	0.22*
Myometrial thickness (mm)	4.1 (0.8)	3.1 (1.4)	0.06*
Presence of an embryo	3 (37.5)	7 (58.3)	0.65**
Fetal heart beat	2 (25)	5 (41.7)	0.64**

Table 4

Comparison of patients’ outcomes.
		Group 1	Group 2	p
		Mean (SD)	Mean (SD)	p
Hospital stay (days)		15.4 (9.5)	11.6 (5.3)	0.31*
Serum β HCG levels resolution time(days)		61.6 (30.3)	30.7 (8.9)	0.006*
Complications	Incomplete uterine rupture	0 (0)	3 (25)	0.24**
	Uterine rupture	1 (12.5)	0 (0)	0.42**
	Transfusion	1 (12.5)	1 (8.3)	0.65**
	Oligo menorrhea	3 (37.5)	7 (58.3)	0.65**

This study showed that CSP is a rare form of ectopic pregnancy (1.14% of cases). Most of patients (60%) were asymptomatic and presenting for isolated amenorrhea. Diagnosis was made on ultrasonographic criteria in all cases. When comparing two groups of patients treated respectively with MTX systemic injection with DC and UAE with DC, the second management strategy was associated with a shorter hospital stay duration and a shorter shorter resolution time of serum βHCG levels. There was no statistical significance between the two groups with respect to complications.

The clinical Implication of this study was to report the clinical and evolutionary characteristics of CSP, which is still a relatively rare and complex form of ectopic pregnancy although its incidence is constantly increasing. Moreover, we compared in our study two management strategies of CSP with respect to patients’ outcomes. In fact, there is no actual consensus on the management algorithm of CSP because of the limited number of studies.

CSP was first described by Larsen and Solomon in 1978 [1]. Priorly considered to be one of the rarest forms of ectopic pregnancies, the incidence of CSP has been rising during the last decade, due to a threatening increase in the rate of cesarean deliveries [2]. The frequency of CSP was reported in the literature as ranging from 0.015–1.3% of total ectopic pregnancies [3–5]. Similarly, the frequency of CSP reported in our study was 1.14% of all ectopic pregnancies.

The main independent risk factors reported by Zhou et al. were maternal age over 35 years, higher gravidity, parity, and higher number of induced abortions [6]. Half of our patients were aged over 35 years old. However, the different reports were contradictory in regards to the correlation between the number of prior CD, and the incidence of CSP. In fact, Jurkovic, et al. reported that 72% of CSP patients had undergone at least two cesarean procedures [7]. In our study, 80% of patients underwent 2 or more CDs. Other risk factors were reported in literature such as history of myomectomy, peri partum infections, previous CSP, retroflexion of the uterus, and prolonged labor [8–10]

Sixty percent of our patients were asymptomatic when diagnosed with CSP. Grechukhina et al. also showed that 61% of patients were asymptomatic at diagnosis. The main symptoms reported in this study were vaginal bleeding and pelvic pain [11]. Most of studies showed that the majority of patients had stable vitals at admission [12, 13].

Mean serum βHCG levels mostly ranged from 10000 mUI/ml to 50000 mUI/ml in the reported studies [5, 11, 13, 14]. Ultrasonography provides a clear diagnosis of CSP. Endovaginal ultrasound examination was reported to be the major diagnostic tool with a high sensitivity of 84.6% [12, 15] .

Timor –Tritsh et al. described, in 2019, two implantation modes of CSP: “on the scar” with a measurable myometrial thickness between the placenta and/or the gestational sac and the anterior uterine wall or the bladder ( usually ≥ 2–3 mm) ; “in the niche” with no measurable myometrium between the placenta and/or the gestational sac and the bladder (less than 2 millimeters of uterine wall left) [12]. Kaelin- Agt, A et al. proved in a retrospective study published in 2017 that “ in the niche “ CSPs were more likely to result in uterine rupture and massive bleeding leading to hysterectomy if not diagnosed and treated early [22]. The average myometrial thickness in our study was 3.5 millimeters (1.2 mm), and 35% of CSP were classified as "in the niche."

Studies showed that there has been no consensus on the algorithm of the management of CSP and further series with large samples are necessary. The reported management strategies included expectant, medical, local treatment, and surgical approaches. In all cases, an early management is necessary to avoid life-threatening complications.

The expectant management of CSP is extremely rare and not recommended by most of the authors [23]. When compared to systemic methotrexate injection, ultrasound-guided MTX injection into the gestational sac was found to be highly efficient, with shorter treatment duration and fewer side effects [24].

Bodur et al. reported an 85% success rate for systemic MTX injection if the gestational age was less than 8 weeks, there was no fetal heart beat detected, and the initial serum -HCG level was less than 12000 mUI/mL [25]. The reported gestational age for patients receiving systemic methotrexate in our study was 6,7 weeks (1.3), and no fetal heart beat was detected in 75% of cases, but the reported mean -HCG serum levels were higher (470,15,7 mUI/ml).

Maheux Lacroix et al. showed better management outcomes when combining local and systemic injections of MTX [17]. However, other studies reported that UAE associated with DC was significantly more efficient than other management strategies, with better success rates and fewer complications [18]. In fact, shorter resolution time of serum HCG levels, shorter duration of hospital stay and less blood loss have been reported with UAE associated with DC. Similarly, our study showed a significantly shorter resolution time of serum βHCG levels in patients managed with UAE and DC (p = 0.006). A shorter hospital stay duration was also reported, but with no statistical significance (p = 0.31).

Reports were controversial as to the complications observed with each therapeutic option. Giampaolino et al. reported that UAE followed by DC was associated with a higher risk of complications (90%) regardless of the gestational age [19]. In our study, more complications were found in patients treated with UAE and DC but there was no statistical significance. Chen et al. reported less menstrual flow and duration in patients treated by UAE and DC [20].

Our study was conducted over a long period of time, allowing us to report the evolutionary characteristics of this rare condition, as well as outcomes in two management groups. However, this was a retrospective study with a small sample size, a lack of information about the indications for previous caesarean deliveries, the duration between the previous cesarean and the CSP and the estimated blood loss during DC were the major limits of our study.

The real incidence of CSP is still unknown, but the increasing number of studies and articles published during the last ten years should raise gynecologists’ and obstetricians’ awareness about the importance of early diagnosis and management of this condition. In our study, we reported that the CSP was more common in women aged 35 years or more with at least 2 previous cesarean deliveries. We concluded that UAE associated with an ultrasound-guided DC may be an interesting treatment option with fewer limitations for the follow up and less duration of hospital stay.

ETHICS APPROVAL AND CONSENT TO PARTICIPATE:

The study was approved by the ethics committee of HEDI CHAKER UNIVERSITY HOPITAL, TUNIS.

Approval was granted by HEDI CHAKER UNIVERSITY HOPITAL LOCAL ETHICS COMMITTEE (ID: 01058291) (Approval date: 12.07.2022).

All methods were performed in accordance with the relevant guidelines and regulations set out by the Declaration of Helsinki.

An informed consent was obtained from all participants. Proof of consent to participate can be requested at any time.

CONSENT FOR PUBLICATION:

Not applicable.

AVAILABILITY OF DATA AND MATERIALS:

The datasets generated and analyzed during the current study are not publicly available due to patient privacy but are available from the corresponding author.

COMPETING INTERESTS:

The authors declare that they have no competing interests.

FUNDING:

No Funding was received.

AUTHORS’ CONTRIBUTIONS

MF, FK, MD contributed to the study design, data collection and data analysis.

FC, BA contributed to manuscript writing and review.

KC, critically revised the manuscript.

All authors read and approved the final manuscript.

ACKNOWLEDGEMENTS:

Not applicable.

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No competing interests reported.

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Version 1

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Cesarean scar pregnancy: a ten-year single center experience

Status:

Version 1

Abstract

Introduction:

Patients and methods:

Results:

Conclusion:

INTRODUCTION

PATIENTS AND METHODS

Patients:

Statistical analysis:

RESULTS

DISCUSSION

CONCLUSION

Declarations

References

Additional Declarations

Status:

Version 1