Critically Appraised Topic: Which Type of Treatment for First Trimester Pregnancy Loss is Most Efficacious?
Summary of methods/findings:
Study #1: This was a randomized controlled trial of 1200 patients from 7 hospitals in the UK from May 1997 to December 2001. Patients were eligible if they were <13 gestation with a diagnosis of early fetal demise or incomplete miscarriage. Exclusion criteria included severe hemorrhage or pain, temp > 37.5℃ (99.5℉), severe asthma, hemolytic disease/blood dyscrasias, current anticoagulation or systemic corticosteroid treatment, twin or higher order pregnancy, smoker over 35, or inability to understand written English. The objective of the study was to determine whether a clinically important difference exists between expectant, medical, and surgical management of miscarriage defined by their primary outcome of confirmed gynecological infection within 14 days and at eight weeks. Multiple secondary outcomes studied included treatment with antibiotics, duration of clinical symptoms, and complications. Efficacy was defined as a successful outcome as no unplanned surgical intervention within eight weeks, psychological outcomes, and return to normal activity. Findings included no statistically significant difference in incidence of confirmed infections between the three groups (expectant v surgical group risk difference 0.2%, 95% CI -2.2% to 2.7% and medical v surgical group risk difference 0.7%, CI -1.6% to 3.1%). However, the authors did find that when compared to the surgical group, unplanned hospital admissions and surgical interventions were higher in the expectant group and medical groups and specifically in the expectant group (risk difference -39%, CI -44% to -34%) more so than medical group (risk difference -30%, CI -35% to -25%).
Study #2: This was a retrospective cohort study of 404 participants that examined manual vacuum suction aspiration compared with dilation and curettage (D&C) and electric vacuum aspiration for miscarriage. The study was conducted from January 2014 to December 2018 at the International University of Health and Welfare Hospital in Tochigi, Japan. Inclusion criteria was that participants had to be within the first 12 weeks of pregnancy. Exclusion criteria included suspected ectopic or molar pregnancies, or suspected completed spontaneous abortion. The primary outcomes were duration of surgery, amount of anesthetic used, amount of bleeding, incomplete abortion requiring repeat procedures, and severe intra- or postop complications. The results showed no statistical difference between outcomes among the three groups for the first four objectives. There were no severe complications in any of the groups (fifth respective objective).
Study #1: Strengths include that this study was a large multicenter trial that included 7 hospitals with randomization to study arm. At the time the study took place, the conventional management/gold-standard for first trimester miscarriage was surgical intervention so this study’s results show that medical and expectant to be reasonable options given no difference in infection rates. Although it was a large multicenter trial, limitations of the study were due to it being underpowered; the study needed 1422 participants to have 80% power to detect the treatment effect significant at the 5% level but only had 1200. The decreased n was related to challenges in recruiting and of the 3905 women recruited, only less than 1/3 were randomized after 1/3 were ineligible and 1/3 refused which could possibly lead to selection bias. They also compared surgical to expectant and surgical to medical but did not compare expectant to medical.
Study #2: Strengths include that this was a recent study, published in 2020, and it is also one of few studies on this topic. Their cohort groups were similar and no statistical differences. Limitations include that the authors do not discuss other management options such as expectant or medical management in their discussion. Another limitation was that this was a retrospective cohort study which is not the highest quality of study and the fact that they analyzed each group according to different years, not during the same time frame. D&C were performed Jan 2015 to March 2015. Electric vacuum aspiration was performed between April 2015 and May 2016, and MVA were conducted from June 2016 to December 2018. The lack of overlap during these time frames causes concerns such as who performed the three different procedures, what was their level of training, and what else possibly changed during these discrete time frames? The study says participants were randomized but if the Hospital only offered one type of procedure depending on what year it was, how is that true randomization? The study also never mentions how many participants were needed to achieve their goal for power to detect treatment effect or what that goal was. Retrospective studies in general also are subject to information bias due to possible missing information when using existing records.
How would you improve the study design?
Study #1: Areas of improvement that are recommended include increasing sample size so that study would not have been underpowered. The authors mentioned difficulty in recruiting and increasing the length of their study for more enrollment, but another idea would be to involve additional medical centers/hospitals versus solely extending the timeframe for enrollment. Increasing enrollment timeframe could have led to changes management over time which could have led to bias. Another opportunity to for improvement would be to statistically analyze the expectant and medical groups to one another rather than only looking at two discrete groups of surgical versus expectant and surgical versus medical treatment arms. One way to have accomplished this would have been to calculate percentage success rates and confidence intervals for each intervention to see if they intervals overlap or not. If they do, there is no difference, if they do not, there is a statistically significant difference.
Study #2: Recommendations for improvement include changing the study type to a prospective randomized clinical trial and to enroll participants to all three study arms simultaneously versus performing the arms during distinct different time periods. A more comprehensive analysis between patient backgrounds should also be explored as this study only mentioned age, pregnancy history, and gestational age at time of procedure. It would also be useful to expand outcomes to include cost, length of stay, pain, and outcomes at a time interval in the order of several months post-procedure to evaluate for the presence or absence of delayed complications. Additionally, it would be prudent to calculate the number of participants needed to enroll to achieve a predetermined power.
Conclusions: First trimester pregnancy loss is a common diagnosis in the Emergency Department and the ability to educate patients about the current literature regarding the different treatment options is essential. Based on my review of literature, while there is no difference in infection, psychological, or duration of time it takes to return of normal activities, there is a slightly higher risk of unplanned surgery and prolonged bleeding with expectant and medical management in comparison to surgical management. Manual vacuum aspiration is a very promising alternative to standard surgical techniques and appears to be as effective. However, more research needs to be conducted, specifically regarding the use of surgical options such as manual vacuum aspiration within the setting of the Emergency Department to be able to assess this option more objectively and more accurately in direct comparison to expectant or medical management.
Trinder J, Brocklehurst P, Porter R, Read M, Vyas S, Smith L. Management of miscarriage: expectant, medical, or surgical? Results of controlled trial (miscarriage treatment (MIST) trial). BMJ. 2006 May 27;332(7552):1235-40. : 10.1136/bmj.38828.593125.55. 2006 May 17. PMID: 16707509; PMCID: PMC1471967.
Kakinuma T, Kakinuma K, Sakamoto Y, Y, Saito K, Ihara M, Matsuda Y, Sato I, Ohwada M, Yanagida K, Tanaka H. Safety and efficacy of manual vacuum suction compared with conventional dilatation and sharp curettage and electric vacuum aspiration in surgical treatment of miscarriage: a randomized controlled trial. BMC Pregnancy Childbirth. 2020 Nov 16;20(1):695. : 10.1186/s12884-020-03362-4. PMID: 33198679; PMCID: PMC7667767.