Comparative Efficacy of Ethacridine Lactate, Foley’s Catheter, and Mifepristone-Misoprostol for Second-Trimester Termination in Women with Poor Bishop Scores

Introduction

Second-trimester termination of pregnancy (TOP), defined as termination between 13 and 28 weeks of gestation, accounts for a smaller proportion of total abortions but contributes disproportionately to abortion-related morbidity and mortality worldwide [1,2] Although most abortions globally occur in the first trimester, procedures performed in the second trimester are associated with higher risks of hemorrhage, infection, uterine injury, and retained products of conception [3,4] These risks are particularly significant in settings where access to skilled providers, appropriate monitoring, and emergency obstetric care is limited Delays in diagnosis of fetal anomalies, late recognition of pregnancy, or barriers to accessing care often contribute to women presenting in the second trimester, further compounding the clinical and public health burden [6,7]. The risks associated with second-trimester TOP are further amplified in women presenting with an unfavorable cervix, reflected by a low Bishop score (<6), where cervical resistance leads to prolonged induction times, an increased need for adjunctive interventions, and higher complication rates An unripe cervix is less responsive to uterotonic agents, resulting in delayed cervical dilation and inefficient uterine contractions. This may necessitate repeated dosing of medications, combination regimens, or conversion to surgical evacuation. Prolonged induction not only increases patient discomfort and hospital stay but also raises the likelihood of infection and excessive bleeding [9,10]. Therefore, effective cervical ripening and induction strategies are crucial to ensure timely and safe outcomes in this subgroup of patients

Pharmacological methods have increasingly become the mainstay of second-trimester TOP. Current international guidelines recommend the combined use of mifepristone followed by misoprostol, citing high success rates, shorter induction-to-abortion intervals, and a reduced need for surgical intervention [12,13]. Mifepristone, an antiprogestin, blocks progesterone receptors, leading to decidual necrosis, cervical softening, and increased uterine sensitivity to prostaglandins. Subsequent administration of misoprostol, a prostaglandin E1 analogue, stimulates uterine contractions and cervical dilation [ This sequential regimen has consistently demonstrated superior efficacy compared to misoprostol alone, with higher rates of complete expulsion within 24hs and fewer total doses required. Additionally, the combination approach is associated with lower overall complication rates and improved patient satisfaction due to shorter and more predictable induction courses.

Despite its proven effectiveness, access to mifepristone remains limited in many low- and middle-income countries because of cost constraints, regulatory barriers, and its inconsistent availability. In such contexts, providers must rely on alternative regimens that are affordable, accessible, and feasible within the existing health system capacities. Misoprostol alone, though effective, may require higher cumulative doses and longer induction times, particularly in women with an unfavorable cervix. [15].

In resource-limited settings, mechanical and older pharmacological methods continue to play a significant role. Extra-amniotic ethacridine lactate (Rivanol) has historically been used for mid-trimester termination because of its affordability, ease of storage at room temperature, and perceived safety, particularly regarding the risk of uterine rupture It induces abortion through local irritation and stimulation of uterine activity following instillation into the extra-amniotic space. Similarly, Foley’s catheter balloon traction offers a mechanical method of cervical ripening that is inexpensive and widely available, and is often used alone or in combination with misoprostol By exerting direct pressure on the internal cervical os, the balloon promotes endogenous prostaglandin release and gradual cervical dilation. These methods remain important alternatives where newer pharmacological agents are inaccessible, underscoring the need for context-specific, evidence-based approaches to optimize safety and effectiveness in second-trimester TOP.

Methods

Study Design and Setting

This retrospective comparative study was conducted at the Department of Obstetrics and Gynecology at Rajarajeshwari Medical College and Hospital, Bangalore, a tertiary care teaching institution catering to both urban and semi-urban populations. The hospital serves as a referral center for high-risk obstetric cases, including second-trimester pregnancy terminations due to fetal death and congenital anomalies. The study period was from July 2020 to August 2022. During this interval, all eligible cases of second-trimester termination that met the predefined inclusion criteria were identified from departmental registers and hospital electronic medical records.

The retrospective design enabled the evaluation of real-world clinical practices and outcomes across different induction methods routinely employed in our department. Institutional protocols for second-trimester termination were standardized, and management decisions were documented in patient case files. Ethical clearance for the study was obtained from the Institutional Ethics Committee prior to the data extraction. Patient confidentiality was strictly maintained throughout the study, and the data were anonymized during the analysis.

Study Population

The study population comprised women aged > 18 years who presented with singleton pregnancies between 13 and 28 weeks of gestation and required termination due to intrauterine fetal death (IUFD) or confirmed lethal fetal anomalies. Gestational age was determined based on the reliable last menstrual period, corroborated by first- or second-trimester ultrasonography findings.

Only women with an unfavorable cervix at admission, defined as a Bishop score of less than 6, were included in the analysis. The Bishop score was assessed by an experienced obstetrician and included the evaluation of cervical dilatation, effacement, consistency, position, and fetal station. The decision to include only women with low Bishop scores ensured homogeneity in cervical status and allowed for a meaningful comparison of cervical ripening and induction efficacy across the three methods.

Exclusion criteria were established to eliminate confounding clinical conditions that could independently influence the induction outcomes or increase the risk of complications. Women with multiple gestations were excluded because uterine overdistension may have altered contractility patterns. Patients with active pelvic infection, clinical chorioamnionitis, or systemic infection were excluded to avoid exacerbating infectious morbidity. Patients with a low-lying placenta or placenta previa were excluded due to the increased risk of hemorrhage. Women with a previous uterine scar, including a prior cesarean section or myomectomy, were also excluded to minimize the risk of uterine rupture and maintain uniform safety parameters across the study groups.

Intervention Protocols

Eligible participants were categorized into three groups based on the induction method recorded in their medical records. The choice of induction method was determined by the attending consultant according to the departmental protocol, clinical assessment, drug availability, and patient preference when applicable.

Group A: Extra-amniotic Ethacridine Lactate

Patients in Group A received extra-amniotic instillation of 0.1% ethacridine lactate (EAL). The dosage administered was calculated as 10 ml per week of gestational age. Under aseptic precautions, a Foley catheter was introduced transcervically into the extra-amniotic space. The calculated dose of ethacridine lactate was instilled slowly, and the catheter was clamped to retain the solution in the bladder. Patients were monitored for uterine activity, vital signs, and adverse reactions during the study.

If adequate uterine contractions were not achieved within six hours of instillation, intravenous oxytocin infusion was initiated using a standardized incremental regimen. The oxytocin infusion rate was gradually increased until adequate uterine contractions (defined as three to five contractions in 10 min, each lasting 40–60 s) were established. Continuous maternal monitoring was performed throughout the induction process.

Group B: Foley Catheter Plus Misoprostol

Group B underwent mechanical cervical ripening using a 16F intracervical Foley catheter. The balloon was inflated with sterile saline (typically 30–50 ml), and gentle traction was applied by taping the catheter to the inner thigh. This mechanical pressure promotes endogenous prostaglandin release and gradual cervical dilation.

Following catheter insertion, patients received 400 µg of misoprostol intravaginally. Subsequent doses of 200 µg were administered orally every six hours until expulsion or the maximum recommended dose was reached. Patients were monitored for uterine contractions, bleeding, gastrointestinal side effects, and hyperstimulation signs.

If expulsion did not occur after a predefined number of doses or if contractions were inadequate, oxytocin augmentation was initiated at the discretion of the obstetrician.

Group C: Mifepristone Plus Misoprostol

Group C patients received oral mifepristone (200 mg) as a priming agent. After a waiting period of 36–48 h, 400 µg of misoprostol was administered intravaginally. Subsequent oral doses of 200 µg were given every six hours until complete expulsion of the fetus and placenta.

Patients were monitored for uterine contractions, bleeding, and systemic side effects, such as fever, nausea, vomiting, or diarrhea. The timing of misoprostol administration and dosing intervals adhered to departmental guidelines, consistent with contemporary evidence-based practice.

Monitoring and Outcome Measures

All patients were admitted to the labor ward for continuous monitoring during the induction process. Maternal vital signs, including pulse rate, blood pressure, temperature, and uterine contraction pattern, were assessed and documented at regular intervals to ensure maternal safety and evaluate the progress of induction. Periodic vaginal examinations were performed to monitor cervical dilatation and effacement, assess the progression of labor, and confirm the complete expulsion of the fetus and placenta.

The primary efficacy outcomes evaluated in the study included successful abortion within 24 hours, successful abortion within 48 hours, and the induction-to-abortion interval, defined as the duration from initiation of the induction method to complete expulsion. Successful abortion was defined as the complete expulsion of the fetus and placenta without the need for surgical intervention. Secondary outcomes included the requirement for oxytocin augmentation to establish or strengthen uterine contractions, the need for surgical evacuation in cases of incomplete abortion or retained placenta, and the occurrence of major complications, such as excessive hemorrhage or uterine rupture.

Statistical Analysis

Data were entered into Microsoft Excel and analyzed using the IBM SPSS Statistics software (version 25). Continuous variables, including maternal age, gestational age, and induction-to-abortion interval, were expressed as the mean ± standard deviation. One-way analysis of variance (ANOVA) was used to compare the continuous variables across the three groups. When ANOVA demonstrated statistical significance, Tukey’s post-hoc test was applied to identify specific intergroup differences. Categorical variables, such as parity (nulliparity), need for oxytocin augmentation, success rates at 24 and 48 h, and surgical evacuation rates, were analyzed using Pearson’s chi-square test. A p-value of less than 0.05 was considered statistically significant.

Results

The baseline demographic characteristics of the study population demonstrated a high degree of comparability between the three intervention groups. The mean maternal age was similar in the ethacridine, Foley plus misoprostol, and mifepristone plus misoprostol groups, with no statistically significant differences observed (p = 0.480). This homogeneity in age distribution is important because maternal age can influence uterine responsiveness and cervical compliance. The absence of significant variation minimizes the likelihood that age-related physiological differences contributed to the disparities in induction outcomes. Similarly, the proportion of nulliparous women was nearly identical across the three groups (p = 0.995), indicating a comparable parity distribution. Since parity is a known determinant of cervical favourability and labor progression, similar nulliparity rates strengthen the internal validity of the study by ensuring that cervical response patterns were not inherently biased toward one group.

In contrast, the gestational age at induction differed significantly among the groups (p = 0.003). The Foley plus misoprostol group had the highest mean gestational age (20.91 weeks), whereas the mifepristone plus misoprostol group had the lowest mean gestational age (17.07 weeks). This statistically significant variation may reflect clinical decision-making practices, as mechanical methods are sometimes preferred in later gestations. Although gestational age can influence uterine contractility and induction duration, the other baseline characteristics and safety parameters were evenly distributed, indicating an overall comparability. Except for gestational age, no significant baseline differences were identified between the study groups (Table I).

Safety outcomes were similarly distributed across the three groups. The requirement for oxytocin augmentation did not differ significantly, although it was more frequently observed in the ethacridine group. This trend may suggest that additional uterotonic support is occasionally required to achieve adequate contraction patterns following chemical induction with ethacridine; however, the difference did not reach statistical significance. Importantly, the surgical evacuation rates were comparable among all groups (p = 0.766), indicating that none of the induction methods was associated with a higher likelihood of incomplete abortion necessitating operative intervention. These findings collectively support the safety equivalence of the three approaches in the study population.

In contrast to the largely comparable baseline and safety outcomes, significant differences emerged in the efficacy parameters. Successful abortion within 24 h was achieved in 76.9% of patients in both the ethacridine and mifepristone plus misoprostol groups, compared to only 46.7% in the Foley plus misoprostol group. This difference was statistically significant (p = 0.005), indicating the superior early efficacy of the pharmacological regimens. By 48 hours, overall success rates improved across all groups; however, the Foley group continued to demonstrate a lower cumulative success rate (86.7%) than that of the ethacridine and mifepristone groups (100 %; p = 0.015). These findings highlight the comparatively slower and less efficient response associated with mechanical methods.

The induction-to-abortion interval further emphasizes these differences. The mean interval was significantly shorter in the mifepristone plus misoprostol (18.27 ± 11.09 hours) and ethacridine (18.35 ± 12.09 hours) groups than in the Foley plus misoprostol group (31.13 ± 18.03 hours) (p = 0.012). Post hoc Tukey’s analysis confirmed that the Foley group had a significantly longer induction–abortion interval than the other two groups (p < 0.05), while no significant difference was detected between the ethacridine and mifepristone groups (p = 1.000) (Table II). Overall, these findings demonstrate that pharmacological methods achieved more rapid and reliable termination outcomes than the mechanical approach without compromising safety. 

Abbreviation 1: Explanation of abbreviation 1; Abbreviation 2: Explanation of abbreviation 2.

Data are presented as mean ± SD or Number (%). P-values derived from ANOVA for continuous and Chi-Square for categorical variables

Discussion

Baseline Characteristics and Comparability

The present study demonstrated good baseline comparability among the three groups with respect to maternal age and parity, thereby minimizing the potential confounding influences on the primary outcome measures. Age and parity are well-recognized determinants of cervical responsiveness and uterine contractility; multiparous women, for example, often experience shorter induction times due to prior cervical remodelling ^[18]. However, in this cohort, the absence of statistically significant differences in these variables suggests that the observed differences in efficacy outcomes are more likely attributable to the intervention methods rather than demographic disparities Similar findings have been reported in comparative studies evaluating second-trimester termination methods, in which age and parity were not found to significantly affect induction outcomes when standardized protocols were followed ^[20,21]. This reinforces the validity of the comparisons made in the present analysis.

Although the gestational age differed significantly among the groups, with the Foley plus misoprostol group presenting at a more advanced gestational age, this variation mirrors real-world clinical practice. In many institutional settings, mechanical methods are preferentially utilized in later gestations due to concerns about uterine hyperstimulation or scar integrity, particularly in women with previous cesarean sections or other uterine surgeries ^[22,23]. Therefore, the distribution observed in this study likely reflects pragmatic decision-making rather than a systematic allocation bias. Importantly, aside from gestational age, other safety-related baseline characteristics, including the need for oxytocin augmentation and surgical evacuation rates, were evenly distributed across the groups. This indicates broadly comparable baseline risk profiles and strengthens the internal validity of comparative outcomes.

Efficacy and Induction–Abortion Interval

A central finding of this study was the significantly shorter induction-to-abortion interval observed in the ethacridine lactate and mifepristone–misoprostol groups compared with the Foley plus misoprostol group. Both the ethacridine and mifepristone regimens achieved mean induction-abortion intervals of approximately 18 h, demonstrating rapid progression from the initiation of active induction to expulsion. These findings are consistent with reports describing enhanced uterine responsiveness following pharmacological priming [24, 25]. Mifepristone acts as a progesterone receptor antagonist, inducing decidual necrosis, cervical softening, and upregulation of prostaglandin receptors, thereby increasing uterine sensitivity to misoprostol [26]. Although it requires a 36-48-hour pretreatment interval before prostaglandin administration, the subsequent active expulsion phase is typically rapid and predictable [12] This biphasic mechanism explains the overall efficiency of the regime, despite the apparent delay before the initiation of misoprostol.

Interestingly, ethacridine lactate demonstrated an active-phase efficiency comparable to that of mifepristone–misoprostol in this study. Traditionally, ethacridine has been perceived as a slower induction agent, largely due to older reports describing prolonged induction durations and variable outcomes However, many of those earlier studies employed non-standardized dosing regimens and inconsistent monitoring protocols [25, 27]. In contrast, contemporary institutional protocols emphasize controlled extra-amniotic instillation, careful patient selection, and timely adjunctive interventions, which may account for the improved performance observed. The comparable mean induction interval of approximately 18 hours challenges the notion that ethacridine is inherently inferior in speed and suggests that, when applied appropriately, it remains a viable alternative in selected populations [28].

In contrast, the Foley catheter plus misoprostol group exhibited the longest induction–abortion interval. Mechanical dilation relies on direct pressure at the internal cervical os to stimulate endogenous prostaglandin release and promote gradual cervical ripening. However, this process may be less synchronized than pharmacological regimens that directly target uterine contractility and cervical remodeling. Previous studies have similarly reported prolonged induction times with mechanical methods, particularly in women presenting with low Bishop scores, where baseline cervical resistance is high [29,30]. The findings of the present study align with this body of evidence and underscore the comparatively slower onset of effective labor with mechanical approaches alone or in combination with misoprostol.

Success Rates

Success within 24 h was significantly higher in the ethacridine and mifepristone groups than in the Foley group, with both pharmacological regimens achieving a 76.9% success rate. By 48 h, complete success was achieved in all patients in the ethacridine and mifepristone groups, whereas the Foley group continued to demonstrate a lower cumulative success rate. These findings are consistent with prior literature demonstrating the superior efficacy of pharmacological or chemo-mechanical regimens over mechanical dilation alone [23, 31-33]. The enhanced success observed in the mifepristone group reflects its well-established role as a uterine priming agent, improving both cervical readiness and contractile efficiency The comparable performance of ethacridine further supports its effectiveness in inducing complete expulsion within an acceptable timeframe. Notably, the lower 24- and 48-hour success rates in the Foley group may be partially influenced by the higher mean gestational age in this cohort. Advancing gestational age has been associated with longer induction durations and decreased responsiveness to induction agents, possibly due to increased uterine distension and altered myometrial sensitivity Although statistical adjustments were performed, residual confounding could not be entirely excluded. From a clinical standpoint, higher early success rates are advantageous for reducing hospital stays, minimizing patient discomfort, and lowering healthcare resource utilization. In settings with limited bed availability and high patient turnover, methods that reliably achieve expulsion within 24–48 h may offer significant operational benefits.

Safety Outcomes

Safety outcomes were broadly comparable across all three groups, with no statistically significant differences in the rates of surgical evacuation. This finding is particularly important because surgical evacuation following failed medical induction can increase the risk of hemorrhage, infection, and uterine trauma. The absence of significant intergroup differences suggests that, when conducted under standardized protocols with appropriate monitoring, second-trimester termination is generally safe regardless of the chosen induction method [35,36]. Although oxytocin augmentation was more frequently required in the ethacridine group, this difference did not reach statistical significance. The higher reliance on adjunctive oxytocin may reflect the need to enhance uterine contractility following chemical irritation induced by ethacridine. However, similar patterns have been reported previously. Espada-Trespalacios et al. observed increased adjunctive oxytocin use in ethacridine-based regimens without a corresponding rise in complications, suggesting that the need for augmentation does not necessarily compromise safety [37]. The present findings are consistent with this observation. Importantly, no cases of severe complications, such as uterine rupture or significant hemorrhage requiring transfusion, were reported. This supports the overall safety profile of all three regimens in appropriately selected patients and underscores the importance of institutional protocols, trained personnel, and timely interventions in mitigating risks.

Clinical Implications

This study contributes valuable comparative data on mechanical and pharmacological approaches for second-trimester termination in women with low Bishop scores. While the mifepristone misoprostol combination remains the gold standard due to its well-documented efficacy and predictable course, the findings indicate that ethacridine lactate can achieve comparable induction intervals and success rates under standardized conditions

In resource-limited settings where access to mifepristone is constrained by regulatory restrictions, cost barriers, or supply chain challenges, ethacridine lactate may represent a practical and effective alternative [39]. Its affordability, stability at room temperature, and long history of use make it particularly attractive in low- and middle-income countries. Furthermore, the absence of significant differences in safety outcomes reinforces its viability as a context-adapted clinical protocol.

The relatively slower performance of the Foley catheter plus misoprostol does not negate its utility. Mechanical methods remain important options for patients with contraindications to prostaglandins or in situations where minimizing pharmacological exposure is desirable. Individualized care considering gestational age, cervical status, comorbidities, and resource availability remains paramount.

Limitation

The retrospective design of this study inherently limits the control over confounding variables and relies heavily on the accuracy and completeness of medical records. Retrospective data collection may introduce information bias and restrict the ability to fully standardize intervention protocols across all cases. Additionally, the relatively small sample size within each intervention group may have reduced the statistical power to detect subtle differences in safety outcomes, particularly in rare adverse events.

The significant variation in gestational age between the groups represents another limitation. Although statistical adjustments were undertaken, gestational age may independently influence induction times and success rates, and residual confounding cannot be excluded. Prospective randomized controlled trials with larger sample sizes and stratification by gestational age would provide more definitive comparative evidence.

Despite these limitations, this study offers meaningful insights into the relative efficacy and safety of commonly used second-trimester termination methods in women with an unfavorable cervical status. These findings support the continued evaluation and optimization of pharmacological and mechanical approaches in diverse healthcare settings.

Conclusions

This study demonstrated that both ethacridine lactate and the mifepristone–misoprostol regimen were significantly more effective and faster than the Foley catheter with misoprostol for second-trimester termination in women with poor Bishop scores. Ethacridine lactate showed induction–abortion intervals and success rates comparable to those of mifepristone, challenging the perception that it is an inferior or slower method of abortion. Safety outcomes were similar across all three methods, with no significant intergroup differences in the need for surgical evacuation or oxytocin augmentation. These findings support the continued use of ethacridine lactate as a safe, effective, and practical alternative in resource-limited settings where access to mifepristone may be restricted.

Declarations

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