RT 2 WK 2 PICO Expanded into Mini-CAT
Clinical Question:
A 21 y/o G2P1001 female with a history of a C-section delivery x 1 and estimated gestational age of six weeks presents to GYN requesting medical abortion treatment for an unwanted pregnancy.
PICO Question:
In first trimester pregnant patients seeking medical abortion treatment for an unwanted pregnancy, is treatment with Misoprostol alone as effective as combination treatment with Mifepristone and Misoprostol?
| P | I | C | O |
| Pregnant patients | Misoprostol | Mifepristone and Misoprostol | Higher efficacy |
| Medical abortion | Misoprostol alone | Combination Mifepristone and Misoprostol | More effective |
| First trimester | Better outcome | ||
Search Strategy:
PubMed
- Search terms: pregnant, medical abortion, Mifepristone, Misoprostol
- Published within the past 5 years [230 results]
- Search terms: pregnant patient, medical abortion, Mifepristone, Misoprostol
- Published within the past 5 years [195 results]
- Search terms: pregnant patient, medical abortion, Mifepristone, Misoprostol, higher efficacy
- Published within the past 5 years [91 results]
Google Scholar
- Search terms: pregnant patient, medical abortion, Mifepristone, Misoprostol
- Published within the past 5 years [2,510 results]
- Search terms: pregnant patient, medical abortion, Mifepristone, Misoprostol, higher efficacy
- Published within the past 5 years [1,480 results]
- Search terms: pregnant patient, medical abortion, Mifepristone, Misoprostol, combination, more effective
- Published within the past 5 years [1,380 results]
Cochrane Library
- Search terms: medical abortion, Mifepristone, Misoprostol
- Published within the past 5 years [2 reviews, 305 trials]
- Search terms: medical abortion, Mifepristone, Misoprostol, better outcome
- Published within the past 5 years [2 trials, 10 trials]
I narrowed down the choices for my selected articles by evaluating which articles specifically studied the impact of Misoprostol alone versus Misoprostol in combination with Mifepristone in the setting of a first trimester medical abortion. I concluded that the articles selected are of high quality evidence, as they include two systematic reviews and two randomized controlled trials. All are also MEDLINE indexed and recently published within the past five years.
Articles Chosen
1. Medical termination for pregnancy in early first trimester (≤ 63 days) using combination of mifepristone and misoprostol or misoprostol alone: a systematic review
Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339463/
Background: A wide range of drugs have been studied for first trimester medical abortion. Studies evaluating different regimens, including combination mifepristone and misoprostol and misoprostol alone regimens, show varying results related to safety, efficacy and other outcomes. Thus, the objectives of this systematic review were to compare the safety, effectiveness and acceptability of medical abortion and to compare medical with surgical methods of abortion ≤63 days of gestation.
Methods: Pubmed and EMBASE were systematically searched from database inception through January 2019 using a combination of MeSH, keywords and text words. Randomized controlled trials on induced abortion at ≤63 days that compared different regimens of medical abortion using mifepristone and/or misoprostol and trials that compared medical with surgical methods of abortion were included. We extracted data into a pre-designed form, calculated effect estimates, and performed meta-analyses where possible. The primary outcomes were ongoing pregnancy and successful abortion.
Results: Thirty-three studies composed of 22,275 participants were included in this review. Combined regimens using mifepristone and misoprostol had lower rates of ongoing pregnancy, higher rates of successful abortion and satisfaction compared to misoprostol only regimens. In combined regimens, misoprostol 800 μg was more effective than 400 μg. There was no significant difference in dosing intervals between mifepristone and misoprostol and routes of misoprostol administration in combination or misoprostol alone regimens. The rate of serious adverse events was generally low.
2. Efficacy of Misoprostol Alone for First-Trimester Medical Abortion: A Systematic Review
Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309472/
Objective: To summarize available data on the effectiveness and safety of single-agent misoprostol for medical abortion in the first trimester.
Data Sources: We searched Medline, CABI, Cochrane, EMBASE, LILACS, and the Web of Science, and ClinicalTrials.gov for English language studies that evaluated misoprostol alone for abortion of viable pregnancy in the first trimester.
Methods of Study Selection: Our search yielded 1562 citations, of which 38 included data from 53 trial groups that met our inclusion and exclusion criteria.
Tabulation, Integration, and Results: We abstracted data about each trial group, including study characteristics, treatment regimen, clinical protocol, number of women treated and followed, and numbers with outcomes of interest. We used meta-analytic methods and logistic regression to examine factors associated with surgical intervention after treatment. Among all 12,829 evaluable women, 2536 (meta-analytic estimate 22.0%, 95% CI 18.8%, 25.5%) had surgical uterine evacuation. Multiple factors were significantly associated with this proportion, including misoprostol amount per dose and route of administration, loss to follow-up rate, publication date, geographic region, number of misoprostol doses, duration of dosing, and time between dosing and evaluation. Of 6359 evaluable women, 384 (meta-analytic estimate 6.8%, 95% CI 5.3%, 8.5%) had ongoing pregnancy. At most 26 of 12,184 evaluable women (meta-analytic estimate 0.7%, 95% CI 0.4%, 1.0%) were transfused or hospitalized for abortion-related reasons. In trials that provided satisfaction data, most of women were satisfied or very satisfied with the treatment (meta-analytic estimate 78%, 95% CI 71%, 85%).
Conclusions: Misoprostol alone is effective and safe and is a reasonable option for women seeking abortion in the first trimester. Research is indicated to further refine the regimen and to establish efficacy in the late first trimester.
Systematic Review Registration: PROSPERO, CRD42018083589.
3. Early medical abortion with self-administered low-dose mifepristone in combination with misoprostol
Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175481/
Aim: The aim of the present study was to investigate the safety and efficacy of low-dose mifepristone combined with self-administered misoprostol for termination of early pregnancy.
Methods: A total of 533 women seeking medical abortion in early pregnancy (≤49 days since the last menstrual period) were divided randomly into hospital- (H-Mis, 250) and self- (S-Mis, 283) administered misoprostol groups. Women in two groups took 100 mg of oral mifepristone in hospital followed by 200 μg of sublingual misoprostol 24 h later in hospital or home. The primary outcome parameter was complete abortion without surgical intervention. Secondary outcomes were uterine bleeding, return of regular menses, side effects and patient acceptability.
Results: High rates of complete abortion were observed for both the H-Mis group (243/250; 94.8%) and the S-Mis group (266/283; 94.0%). No significant differences in outcomes (complete abortion/failure rates) or side effects were observed between the two groups. General satisfaction rates were similar for the two groups (H-Mis, 231/250, 92.4%; S-Mis, 263/283, 92.9%; P > 0.05). Higher convenience of administration (H-Mis, 211/250, 84.4%; S-Mis, 270/283, 95.4%; P < 0.05) and privacy protection (H-Mis, 214/250, 85.6%; S-Mis, 267/283, 94.3%; P < 0.05) satisfaction rates were obtained for the S-Mis group than for the H-Mis group.
Conclusion: Self-administered sublingual misoprostol is as safe and effective as hospital-administered misoprostol following low-dose mifepristone to terminate early pregnancy (≤49 days of amenorrhoea) with fewer side effects.
Key words: early medical abortion, low-dose, mifepristone and misoprostol, self-administration.
4. Mifepristone Pretreatment for the Medical Management of Early Pregnancy Loss
Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437668/
BACKGROUND—Medical management of early pregnancy loss is an alternative to uterine aspiration, but standard medical treatment with misoprostol commonly results in treatment failure. We compared the efficacy and safety of pretreatment with mifepristone followed by treatment with misoprostol with the efficacy and safety of misoprostol use alone for the management of early pregnancy loss.
METHODS—We randomly assigned 300 women who had an anembryonic gestation or in whom embryonic or fetal death was confirmed to receive pretreatment with 200 mg of mifepristone, administered orally, followed by 800 µg of misoprostol, administered vaginally (mifepristone-pretreatment group), or 800 µg of misoprostol alone, administered vaginally (misoprostol-alone group). Participants returned 1 to 4 days after misoprostol use for evaluation, including ultrasound examination, by an investigator who was unaware of the treatment-group assignments. Women in whom the gestational sac was not expelled were offered expectant management, a second dose of misoprostol, or uterine aspiration. We followed all participants for 30 days after randomization. Our primary outcome was gestational sac expulsion with one dose of misoprostol by the first follow-up visit and no additional intervention within 30 days after treatment.
RESULTS—Complete expulsion after one dose of misoprostol occurred in 124 of 148 women (83.8%; 95% confidence interval [CI], 76.8 to 89.3) in the mifepristone-pretreatment group and in 100 of 149 women (67.1%; 95% CI, 59.0 to 74.6) in the misoprostol-alone group (relative risk,1.25; 95% CI, 1.09 to 1.43). Uterine aspiration was performed less frequently in the mifepristone-pretreatment group than in the misoprostol-alone group (8.8% vs. 23.5%; relative risk, 0.37; 95% CI, 0.21 to 0.68). Bleeding that resulted in blood transfusion occurred in 2.0% of the women in the mifepristone-pretreatment group and in 0.7% of the women in the misoprostol-alone group (P = 0.31); pelvic infection was diagnosed in 1.3% of the women in each group.
CONCLUSIONS—Pretreatment with mifepristone followed by treatment with misoprostol resulted in a higher likelihood of successful management of first-trimester pregnancy loss than treatment with misoprostol alone.
Summary of the Evidence:
| Author (Date) | Level of Evidence | Sample/Setting
(# of subjects/ studies, cohort definition etc. ) |
Outcome(s) studied | Key Findings | Limitations and Biases |
| Abubeker FA, Lavelanet A, Rodriguez MI, Kim C (2020) | Systematic review |
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| Raymond EG, Harrison MS, Weaver MA (2019) | Systematic review |
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| Song LP, Tang SY, Li CL, Zhou LJ, Mo XT (2018) | Randomized controlled trial |
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| Schreiber CA, Creinin MD, Atrio J, Sonalkar S, Ratcliffe SJ, Barnhart KT (2018) | Randomized controlled trial |
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Weight of the Evidence
Article 1: All of the articles included in the systematic review were RCTs, which offer high quality evidence. They were also relevant to the clinical question posed and were conducted across different settings, providing generalizable findings. One weakness, however, was that some of the included studies have a high risk of performance and detection bias.
Article 2: Articles included in the systematic review were case studies, randomized trials, or cohort studies. The studies included were also conducted in diverse settings with high rates of follow-up. Various regimens and clinical protocols were included to allow for examination of factors that may lead to the likelihood of surgical intervention following treatment with Misoprostol alone. However, two studies contributed nearly half of the patients, dominating the analysis and potentially affecting the generalizability of the results.
Article 3: The article involved a randomized controlled trial, which provides a high level of quality evidence. It was also published in 2018, providing relevant findings to answer the clinical question posed.
Article 4: The article involved a randomized controlled trial and was published in 2019, providing a high level of evidence and relevance to the clinical question at hand. Additionally, high rates of participant retention and adherence to the protocol were observed. Furthermore, the sample population was diverse in terms of sociodemographic status and pregnancy diagnosis, allowing for generalizable results.
Magnitude of Effect
Article 1: Women treated with a combined regimen had lower rates of ongoing pregnancy (RR 0.16 CI 95% 0.08–0.31, low certainty of evidence) and higher rates of successful abortion (RR 1.23 CI 95% 1.16–1.30, very low certainty of evidence) compared to women treated with a Misoprostol only regimen. The combined regimen resulted in a higher rate of satisfaction compared with Misoprostol only regimen (RR 1.13 CI 95% 1.00–1.26, low certainty of evidence).
Article 2: Among all 12,829 participants, 2536 (meta-analytic estimate 22.0%, 95% CI 18.8%, 25.5%) had surgical uterine evacuation. 384 of 6359 evaluable women (meta-analytic estimate 6.8%, 95% CI 5.3%, 8.5%) had ongoing pregnancy. 26 of 12,184 evaluable women (meta-analytic estimate 0.7%, 95% CI 0.4%, 1.0%) were transfused or hospitalized for abortion-related reasons. In trials that provided satisfaction data, most of women were satisfied or very satisfied with the treatment (meta-analytic estimate 78%, 95% CI 71%, 85%).
Article 3: Success rates for complete abortion were comparably high for the two groups (H-Mis group 243/250; 94.8% vs S-Mis group 266/283; 94.0%), with only 17/533 (3.2%) women overall (7/250 in H-Mis group vs 10/283 in S-Mis group) requiring curettage for incomplete abortion and 13/533 (2.4%) women overall (6/250 in H-Mis group vs 7/283 in S-Mis group) experiencing continued pregnancy post-treatment (confirmed by transvaginal ultrasound). General satisfaction rates were similar for the two groups (H-Mis, 231/250, 92.4%; S-Mis, 263/283, 92.9%; P > 0.05). Higher convenience of administration (H-Mis, 211/250, 84.4%; S-Mis, 270/283, 95.4%; P < 0.05) and privacy protection (H-Mis, 214/250, 85.6%; S-Mis, 267/283, 94.3%; P < 0.05) satisfaction rates were obtained for the S-Mis group than for the H-Mis group.
Article 4: Complete expulsion after one dose of Misoprostol occurred in 124 of 148 women (83.8%; 95% confidence interval [CI], 76.8 to 89.3) in the Mifepristone-pretreatment group and in 100 of 149 women (67.1%; 95% CI, 59.0 to 74.6) in the Misoprostol-alone group (relative risk,1.25; 95% CI, 1.09 to 1.43). Uterine aspiration was performed less frequently in the Mifepristone-pretreatment group than in the Misoprostol-alone group (8.8% vs. 23.5%; relative risk, 0.37; 95% CI, 0.21 to 0.68). Bleeding that resulted in blood transfusion occurred in 2.0% of the women in the mifepristone-pretreatment group and in 0.7% of the women in the misoprostol-alone group (P = 0.31); pelvic infection was diagnosed in 1.3% of the women in each group.
Clinical Significance
Article 1: Women with an unwanted first trimester pregnancy may safely and effectively terminate their pregnancy with combined medical treatment of Mifepristone and Misoprostol.
Article 2: Misoprostol alone is an appropriate course of treatment for first trimester medical abortion for women limited by access or cost despite decreased efficacy compared to combined regimens with Mifepristone-Misoprostol.
Article 3: Self-administered Misoprostol is favored over hospital-administered Misoprostol and can reduce treatment costs while giving patients control over the timing of abortion induction.
Article 4: The standard 800 µg dose of Misoprostol administered vaginally has been found to have low efficacy among women with a closed cervical os with 15-40% requiring a second dose. This can either prolong the treatment period or require uterine evacuation, which had been the procedure intended to avoid with medical management. Therefore, this rate of failure makes this treatment strategy less clinically useful in practice.
Other Considerations
Article 1: Assessment of patient satisfaction is important to consider in the medical management of first trimester abortion.
Article 2: Access and cost of treatment must also be considered for women wishing to terminate unwanted pregnancy in the first trimester.
Article 3: Although this article did not directly compare Misoprostol alone versus Mifepristone combined with Misoprostol, I chose this article because it notes the efficacy of the combined regimen and suggests self-administration may reduce costs and in turn lead to greater access for patients. This is beneficial for patients who would otherwise take Misoprostol alone, which as the article states, is less effective despite being a safe alternative.
Article 4: This article discusses early pregnancy loss rather than termination of an unwanted pregnancy. However, I included this article because it nonetheless evaluates Misoprostol alone versus the combination of Mifepristone-Misoprostol in safely and effectively managing first trimester abortion for women with a closed cervical os. This article also addresses the fact that Misoprostol can be self-administered, allowing greater comfort and privacy when tissue expulsion occurs.
Conclusion(s):
Article 1: Women who were treated with the combined regimen of Mifepristone and Misoprostol had lower rates of ongoing pregnancy and higher rates of successful abortion compared to women who were treated with Misoprostol alone. Women treated with the combined regimen also reported a higher rate of satisfaction compared with the Misoprostol only regimen.
Article 2: While less effective than combined Mifepristone-Misoprostol treatment, treatment with Misoprostol alone is a reasonable alternative for medical management of first trimester abortion, especially for women with limited access or finances to obtain the combined regimen.
Article 3: Self-administration of low-dose Misoprostol is safe and efficacious, leading to comparably high satisfaction rates as hospital-administered Misoprostol and is more preferred.
Article 4: In the management of early pregnancy loss, pre-treatment with Mifepristone followed by Misoprostol resulted in a higher likelihood of prompt and effective treatment of early pregnancy loss than Misoprostol use alone.
Overall conclusion: While Misoprostol alone has been found to be a reasonably safe and effective method for first trimester medical abortion for patients with limited accessibility to Mifepristone, it is ultimately less effective than the combined regimen of Mifepristone and Misoprostol. Therefore, combined treatment with Mifepristone and Misoprostol is the optimal treatment for patients who are able to obtain such treatment for first trimester medical abortion.
Clinical Bottom Line: In first trimester pregnant patients seeking medical abortion treatment for an unwanted pregnancy, treatment with Misoprostol alone is not as effective as combination treatment with Mifepristone and Misoprostol. The combined regimen is more effective with lower rates of ongoing pregnancy and higher rates of successful abortion compared to Misoprostol alone. Therefore, I would recommend the combined regimen of Mifepristone and Misoprostol to patients who desire early first trimester medical abortion for an unwanted pregnancy so long as it is accessible to them.
