Outcomes of incomplete abortion related to treatment modality

doi:10.21203/rs.3.rs-2617716/v1

Purpose: This study evaluated the differences in treatment outcomes between misoprostol and surgical evacuation in the management of incomplete abortion.

Methods: This retrospective cohort study compared patients with clinical diagnosis of incomplete abortion who underwent surgical or pharmacological (misoprostol) intervention, between the years 2014–2017. Demographics, sonographic results, treatment follow-up, and post-intervention data on retained products of conception were retrieved. A comparison was made between women with incomplete abortion who underwent surgical versus pharmacological intervention.

Results: Among 589 spontaneous abortions, 198 were included in the study, of which 123 (62.1%) underwent surgical evacuation, and 75 (37.9%) pharmacological intervention with misoprostol. Baseline characteristics were similar between groups. During 130.8 ±91.7 days of follow-up, no patient who underwent surgical evacuation had retained products of conception or needed surgical hysteroscopy. Four cases (5.3%) in the misoprostol group had retained products of conception and needed hysteroscopy (p=0.02). Patients who underwent surgical evacuation had higher haemoglobin levels during follow-up (12.1 mg/dl vs. 11.7 mg/dl, p=0.05). No differences between groups in post-treatment pregnancy rates.

Conclusion: Long-term follow-up after incomplete abortion showed that hemodynamically stable patients treated with misoprostol achieved the desired results in 95% of cases without any clinical changes in haemoglobin level or pregnancy interval.

Hysteroscopy

Incomplete abortion

Misoprostol

Retained products of conception

Early pregnancy loss (EPL) is a common occurrence that affects up to 10–25% of pregnancies [1], [2]. Most cases occur during the first trimester (0–13 weeks) [3] before the fetus can survive outside of the womb [1]. EPL is a broad term that encompasses different clinical subcategories including anembryonic gestation, embryonic death, missed abortion, and incomplete abortion. Incomplete abortion occurs when the products of conception (POC) fail to evacuate the uterus completely despite dilation of the cervix. Products of conception (POC) must be removed to prevent haemorrhage, infection, and structural damage [2]. Traditionally, this is achieved by expectant management, pharmacological intervention, or surgical evacuation [4].

Expectant management and pharmacologic management are selected for stable patients with sub-menstrual bleeding [3, 4]. Expectant management is an option for women who prefer to wait for the POC to exit the uterus naturally in the absence of medical intervention. However, expectant management is limited as a treatment option, as risks such as uterine bleeding, infection, and/or failure to conceive thereafter have been shown to outweigh the benefits [2], [5, 6].

Pharmacological management is typically accomplished with misoprostol, a synthetic prostaglandin E1 analogue used to activate myometrial contractions and induce abortion [1]. Misoprostol is administered orally or vaginally, sometimes in sequential doses until a complete abortion is achieved [1], [7]. For many patients, pharmacological intervention is a better option since it is less expensive [1] and less invasive than surgery, which has been associated with uterine perforation, adhesions, trauma, post-surgical infections, and anaesthetic complications [7]. Misoprostol, however, can cause excessive haemorrhage, gastrointestinal upset, abdominal pain, and prolonged follow-up [1]. Moreover, 15–40% of patients are unresponsive to the standard dose and require additional dosing or surgical evacuation [2]. A comparison of surgery to vaginal and oral misoprostol for EPL found that the two treatments were similarly effective in achieving complete abortion, but those who received surgery reported less haemorrhagic episodes and fewer gastrointestinal symptoms [1]. Therefore, surgery, despite its risks, is indicated for women with unstable vital signs, massive vaginal bleeding, and those not interested in prolonged treatment [2].

Much of literature and many of the protocols focus on the management of EPL [2–9]. As such, only a few studies have focused directly on the management incomplete abortion [1, 10]. Therefore, much of what is known about management of incomplete abortions is an extrapolation of data from a broader topic [11] or from studies on different clinical scenarios such as missed abortion [3]. The purpose of this study, therefore, is to observe the most effective management for cases of incomplete abortion exclusively to enhance our understanding of a subject that is less often directly considered.

This is a retrospective cohort study, in which cases of spontaneous incomplete abortion documented from the years 2014–2017 were selected from the electronic medical records of the Obstetrics and Gynecology department at our tertiary medical center.

Data collected from electronic medical records included patient demographics such as gravidity, parity, mother’s age, gestational age, trimester, and the number of fetuses per gestation at the time of diagnosis. Data also included the number of previous abortions, ectopic pregnancies, caesarean sections, and living children.

A comparison was made between women with a clinical diagnosis of incomplete abortion who underwent surgical versus pharmacological intervention with misoprostol during the given timeline.

Surgical evacuation was performed by one-time dilation and curettage (D&C) according to standard practice [12]. Surgical success was measured by comparing the presence or absence of POC on ultrasound performed 4 weeks after surgery at follow-up with patients’ Obstetrician Gynaecologist (Ob-Gyn).

Pharmacological treatment was given with misoprostol especially in cases with low to moderate bleeding. Management of incomplete abortion with misoprostol was based on our department’s protocol for first trimester missed abortion. According to this protocol, women were administered one dose of 400–800 mcg buccal or vaginal misoprostol. Women were seen again after one week and vaginal ultrasound was performed to assess for remaining POC, which would be indication for a second dose of misoprostol according to the same route and dosing protocol. Women were instructed to undergo a second follow up appointment one week later with vaginal ultrasound. At second follow-up, patients with endometrial thickness less than 15 mm with no clear retained product of conception were managed with subsequent follow up vaginal ultrasound after the patients’ next menstrual cycle, during which the uterine contents are shed. Endometrial thickness above 15 mm or clear residua of 10 mm or more was managed with hysteroscopy 2–6 weeks later. This protocol is similar in its parameters of duration for follow-up and dosing to those of other protocols [13].

Haemoglobin levels were measured at the time of diagnosis and after the respective treatments to compare blood loss between groups. Rates of follow-up conception were examined by recording the number of days from day 1 of a failed pregnancy to day 1 of new pregnancy onset among participants.

This study was conducted according to good clinical practice guidelines and was approved by the Meir Medical Center Institutional Review Board. Due to the retrospective nature of the study, informed consent for participation was not required. Patient characteristics were compared between the groups, using student t-test for continuous variables, and chi-square or Fisher Exact Test for categorical variables. Results were considered significant when the p-value was ≤ 0.05. Data are presented as numbers and percentages for categorical variables, and as means and standard deviations for continuous variables. All statistical analyses were performed using IBM SPSS Statistics for Windows.

Five hundred and eighty-nine cases of spontaneous abortion were documented in the electronic medical records from 2014–2017. Among 589 cases reported, 198 (33.6%) of them were listed as incomplete abortions. Of 198 cases of incomplete abortion, 75 (37.9%) of women elected for pharmacological intervention with misoprostol while 123 (62.1%) of women underwent surgical evacuation with D&C.

There was no difference between groups with regard to the haemoglobin levels measured immediately after their release from treatment (10.1 mg/dL vs. 10.7 mg/dL, p = 0.12). However, patients who underwent surgical evacuation had higher haemoglobin levels during follow-up than the misoprostol group (12.1 mg/dL vs. 11.7 mg/dL, p = 0.05).

There were no statistical differences between groups in post-treatment pregnancy rates (p = 0.07). Regardless of treatment, 87 of 198 (43.9%) participants being treated for incomplete abortion successfully achieved pregnancy, 39 (52%) of whom were treated with misoprostol and 48 (39%) who were treated with a D&C.

In this study, we compared outcomes of misoprostol use and surgical evacuation in the management of incomplete abortion using the following outcomes: retained POC following treatments, hysteroscopy following treatments, the duration of treatments, Hb levels before and after treatments, and time between pregnancies in either cohort.

We discovered that during 130.8 ± 91.7 days of follow-up, among 123 patients who underwent surgical evacuation, none had retained products of conception or needed surgical hysteroscopy. Alternatively, four cases (5.3%) in the misoprostol group had retained products of conception and needed hysteroscopy (p = 0.02). These findings are comparable to trends reported in a previous studies, which discovered higher rates of success with surgical evacuation (99%) as compared to misoprostol use (71% with 800 mcg and 84% with a second dose)[3, 11]. Interestingly, however, we documented an even higher rate of success with misoprostol use (95%) in the management of isolated cases of incomplete abortion. This can likely be explained by the pathogenesis of incomplete abortion as the cervix is completely dilated allowing for better expulsion of the uterine products.

Another finding, as predicted, was that treatment for incomplete abortion with misoprostol, in comparison to expeditious surgery, more often resulted in a prolonged course of treatment (e.g., additional doses of misoprostol and/or hysteroscopy (p = 0.02)). Many studies on EPL have observed similar findings, demonstrating an increased rate of follow up with the physician with the use of misoprostol [3, 11, 14]. One study on EPL observed that prolonged treatment with misoprostol was more costly than the surgical alternative since these patients needed additional doses or surgical aspiration [14]. Extended treatment is not benign and can exacerbate emotional and physical discomfort in patients [2]. As such, it should be an important factor to consider when selecting a treatment plan for incomplete abortion as well. Physicians, however, should be mindful that the risk, while possible, is unlikely to result in delays, as demonstrated by the 95% success rate associated with misoprostol use in this study.

Although no significant difference in post-treatment pregnancy rates was noted between those who were treated with misoprostol versus those who underwent surgery, still the medical group had slightly higher rate of post treatment of pregnancies (P = 0.07). This finding is logic since medical treatment without any intra uterine intervention probably would prevent endometrial and intra uterine damage for future implantation. Obviously, we could not prove this difference to be significant and larger studies should be done. While previous studies on EPL have demonstrated similar observations regarding fertility rates after pharmacological therapy as compared to surgical evacuation [15, 16], few have done so in the context of incomplete abortion more specifically as we have demonstrated. This study also suggests that there is no significant correlation between the specific treatment and the patient’s timeline to future conception.

Another parameter used for comparison was the average haemoglobin level measured before and after either mode of treatment. The results showed that patients who underwent surgical evacuation had higher haemoglobin levels at follow-up than those who used misoprostol (12.1 g/dl vs. 11.7 g/dl, p = 0.05) despite having similar baseline haemoglobin values at diagnosis and release. According to the research conducted on EPL, pharmacotherapy with misoprostol is traditionally reserved for patients who are hemodynamically stable as it is more often associated with greater blood loss than aspiration [1]. One study even observed a difference of 3 g/dl in measured haemoglobin between those who were treated with misoprostol and those who underwent surgical aspiration [11], [17]. While extreme differences in haemoglobin levels have been noted previously for cases of EPL, our findings on incomplete abortion, may be less relevant clinically as there was no greater indication for transfusion and management of haemoglobin between groups. Therefore, we presume the management of incomplete abortion with pharmacotherapy to be safe, with no major adverse effects on hemodynamic status.

The most notable strength to this current study is its directed focus on incomplete abortion as opposed to management of EPL more broadly as very little literature exists on the management of incomplete abortion in isolation [1, 10]. Another strength to the study is that the patient population was managed under one strict protocol with careful ultrasound follow-up from a singular institution. Women were also followed throughout the course of their treatment up until achieving a new pregnancy, which allowed us to account for the long-term impact of each treatment respectively on gestation.

This study was limited most notably by its small sample size. Additionally, sampling only from a singular institution may have limited the diversity of population studied in this review. Additionally, the retrospective nature of the study interfered with our ability to control for all confounding factors through randomization and matching.

This study suggests that treatment for incomplete abortion with pharmacotherapy in hemodynamically stable patients should demonstrate complete expulsion in 95% of cases without any clinical changes in haemoglobin level or pregnancy interval. Physicians should consider these results when guiding their patients in the management of an incomplete abortion. It is important that patients understand the possibility of alternative outcomes when being given their options. Further prospective studies with larger sample sizes are required to confirm the outcomes described in this study.

Author’s contributions

Merav Sharvit: Project development, Data analysis, Manuscript editing

Yael Yagur: Data analysis, Manuscript writing and editing.

Rebecca Shams: Manuscript writing.

Yair Daykan: Data analysis, Manuscript editing.

Zvi Klein: Data analysis, Manuscript editing

Ron Schonman: Conceptualized the project, Data analysis, Manuscript editing.

Compliance with Ethical Standards

Funding: This study was not funded.

Conflict of Interest: Author Merav Sharvit declares that she has no conflict of interest. Author Yael Yagur declares that she has no conflict of interest. Author Rebecca Shams declares that she has no conflict of interest. Author Yair Daykan declares that he has no conflict of interest. Author Zvi Klein declares that he has no conflict of interest. Author Ron Schonman declares that he has no conflict of interest.

Ethics approval:All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent: According to the retrospective nature of the study conducted, informed consent was not required from the participants.

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Table 1

Characteristic	Pharmacological intervention (75)	Dilation & curettage (123)	P-value
Age, years	33.5 (± 6.4)	34.6 (± 6.4)	0.16
Parity	1.6 (± 1.1)	2.0 (± 1.9)	0.06
Past history of cesarean section
Zero	58 (77.3%)	99 (81.8%)
One	7 (9.3%)	14 (11.6%)
Two	7 (9.3 %)	7 (5.8%)
Three	3 (4.0%)	1 (0.8%)
Gestational age, weeks	9.5 (± 2.3)	10.5 (± 2.9)	0.01
Trimester
First trimester	73 (97.3%)	102 (83.6%)
Second trimester	2 (2.7%)	20 (16.4%)
Hb at diagnosis	12.0 (± 1.3)	12.2 (±1.4)	0.3

Data are shown as number (%), mean ± standard deviation or median (range), as appropriate;

Table 2

Characteristic	Pharmacological intervention (75)	Dilation & curettage (123)	P-value
Retained POC	4.0 (5.3%)	0.0	0.02
Hysteroscopy	4.0 (5.3%)	0.0	0.02
Hb at release	10.1 (± 1.7)	10.7 (± 1.5)	0.12
Hb at follow-up	11.7 (± 1.1)	12.7 (± 1.3)	0.05
Pregnancy rate	39 (52%)	48 (39%)	0.07
Time between pregnancies, days	145.9 (± 111.4)	117.8 (± 69.4)	0.17

Data are shown as number (%), mean ± standard deviation or median (range), as appropriate;

Product of conception (POC); Haemoglobin (HB)

Outcomes of incomplete abortion related to treatment modality

Status:

Journal Publication

Version 1

Abstract

Introduction

Materials And Methods

Results

Discussion

Conclusions

Declarations

References

Tables

Status:

Journal Publication

Version 1