Reviewer ’s report  
 
Title: Medical termination for pregnancy in early first trimester ( ≤ 63 days) using combination 
of mifepristone and misoprostol or misoprostol alone: a systematic review  
 
Version: 1 Date: 06 Apr 2020  
 
Reviewer: Shanna Elizabeth Williams  
 
Reviewer's report:  
 
This manuscript evaluates the success of combination mifepristone and misoprostol and 
misoprostol alone regimens for medical termination of pregnancies in the early first trimester 
relative to safety, efficacy and other outcomes.  Overall, this is a potent ially interesting topic of 
exploration . However, there are some aspects of this manuscript which require attention.  
 
1.The title of the manuscript lacks specificity.  As the authors note, this systematic review 
focuses specifically on medical termination methods which utilize a combination of mifepristone 
and misoprostol or misoprostol alone.  This should be conveyed in the title.  
 
2.Background (lines 87 -88):  The authors mention that this review was done as part of the 
evidence synthesis for the WHO guid ance on medical abortion.  Are those results available to the 
public? Also, that alone is not enough justification for creating this manuscript.  A more fleshed 
out articulation of the 'value added' of this work would strengthen the background session and 
the overall manuscript.  
 
3.Patient satisfaction is used as a proxy for acceptability.  However, it is not explicitly defined.  
Please add in a few sentences for the reader as to how it was measured.  
 
4. Selection  Criteria (lines 109 -110) Please briefly ar ticulate for the reader why the WHO's 
recommended dosage is 200mg.  
 
5.Data collection and Analysis: The authors mention independent data extraction, assessment of 
risk bias, and disagreement resolution on 3 occasions (Selection Criteria - lines 111 -113; Da ta 
Collection and Analysis - lines 115 -117; 138 -140).  Such reiteration is not necessary.  Please 
reevaluate this repetition.  
 
6.Results: While the data is presented as Risk Ratios, the implications of these values does not 
inform the way the results are presented.  Risk ratios of 1 or close to 1 suggest there is no or little 
difference between the groups being compared.  Meanwhile, confidence intervals which include 
1 indicate that the study was unable to demonstrate a statistically significant difference  between 
the groups being compared.  Twenty -one of the 27 "Efficacy: complete without surgical 
intervention" comparisons have RRs between 0.9 and 1.1 and only 4 of the 27 RRs have CI 
indicating statistically significant differences between the groups compa red.  While greater 
variation around 1 is present for the 27 "Efficacy: ongoing pregnancy" comparisons, only 5 have 
CIs indicating statistically significant differences between the groups compared.  These results 
suggest little to no differences between dr ug combinations relative to regimen, dosage, routes, 
etc. are present. Currently, the results section has a meandering feel to it as a reader by 
presenting all of the findings, both meaningful and meaningless, without differentiating between 
the two, in th e text.  Instead, consider placing all Efficacy results in another table in the main 
document, which can be referred to, but focus on the most meaningful results relative to RR and 
grade in the text itself.  
 
7. Many of the conclusions made in the Discussio n section are overstated or incomplete.  For 
example, suggesting the use of 800 µg of misoprostol in the combined regimen had higher rates 
of successful abortion based on moderate evidence is ONLY true when compared to 400 µg of 
misoprostol.  However, it c urrently reads as if that is true across all dosage amounts. The authors 
precede to contradict this very statement 2 sentences later by acknowledging that 400 µg of 
buccal misoprostol produced higher rates of successful abortion than 800 µg. As the data is  
based on comparisons, results can only be applied relative to each comparison, not in a global 
fashion.   
 
8.As stated earlier, each comparison is independent of the others.  As such, it is inappropriate to 
combine the findings from the dosage, regimen, a nd route sections into the statement made in the 
conclusion (Lines 405 -407: "..a combined regimen of mifepristone and misoprostol containing 
800 µg of misoprostol given 24 hours after mifepristone either vaginally or sublingually was 
found to be an effecti ve, safe and acceptable method for termination of pregnancy ≤ 63 days 
gestation.")  Moreover, most of the comparisons this statement was derived from have RR near 1 
and not significant CIs. The Discussion and Conclusion sections should be updated to reflec t 
more appropriate interpretations of the Results.   
 
Are the meth ods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the c onclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistic al review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, f ees, funding, or salary from an 
organisation that may in any way gain  or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose 
financially from the publication of this manuscript, either now or in the fut ure? 
 
3. Do you hold or are you currently applying for any patents  relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of  the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have  no competing i nterests' 
below. If your reply is yes to any, please give details below.  
 
I declare no competing interests.  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication,  my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal