Reviewer ’s report  
 
Title: Results of a pilot study in the U.S. and Vietnam to assess the utility and acceptabi lity of a  
multi -level pregnancy test (MLPT) for home monitori ng of hCG trends after assisted 
reproduction  
 
Version: 0 Date: 10 Apr 2016  
 
Reviewer: Deborah A. Bartz  
 
Reviewer's report:  
 
This is a descriptive study of the MLPT/SQPT in the se tting of early evaluation following ART 
therapy in 2 REI clinics.  
 
 
 
General comments  
 
1.) In general, I think the authors greatly overstep the limits of their data.  The outcomes that 
are measured are related to acceptability only.  There are no results that  pertain to 
feasibility and there are definitely no results that pertain to improved quality (in fact, 
quite the opposite).  There is no place for any conclusions to be made beyond 
acceptability.  The conclusions of the synopsis, abstract, intro, and discu ssion should 
focus only on acceptability (at least with the results that are currently given)  
 
 
2.) The prior literature quoted in this study (the same literature I am familiar with) refer to 
this technology as SQPT.  The authors themselves switch between te rminology for this 
test, favoring SQPT in the figures and tables and MLPT in the text.  Gynuity often tries to 
drive new terminology.  I don't understand why they are doing it here and would 
recommend 1.) being consistent in your manuscript and 2.) being c onsistent with the 
prior literature that calls this SQPT (my preference).  If you think that in this ART setting 
MLPT is a more appropriate term, you should probably explain why.  
 
 
3.) Throughout the manuscript you refer to this as "two studies."  But you on ly give one 
study protocol and you have all the results combined.  Therefore, this is just one study at 
two different study sites.  Otherwise, I'm reading this expecting to hear "in study 1 we did 
and found X and in study 2 we did and found Y."  I really t hink you should change the 
whole manuscript so that this reads as one study with two study sites.  you even do this 
yourself on occasion  
 
 
4.) Throughout the manuscript you need to explain why the two study locales were chosen, 
what is different about the two populations, what is different about the protocols, about 
the results (including the many results you do list, such as study completene ss and 
protocol deviation) between the two populations and then a comment about the 
significance of the two populations and their results in the discussion.  
 
 
 
Title: this is fairly non -descript with no mention of outcome measured.  If you want to just 
descr ibe its use, you'd have to change the results and the conclusions.  Maybe want to be more 
forthcoming with your title to compel folks to read you work.  
 
 
 
Cover letter:  
 
In the synopsis you say that the SQPT may improve quality of care.  You absolutely have n o data 
to suggest that (in fact, the opposite) and you cannot make this claim.  Please just focus on 
acceptability as this is the only data you have.  
 
 
 
Abstract:  
 
Objectives:  
 
1.) Again, why have both SQPT and MLPT take up precious word real estate in the a bstract?  
 
 
2.) You do not have any results that pertain to feasibility (such as how well the subjects were 
able to adhere to the study procedures).  In fact, you state that in at least two instances 
study procedures had to change to allow for subjects inabil ity to follow the initial study 
protocol.  you give no data on how many SQPT values were missing from the anticipate 
6 per pregnant subject or how many subjects deviate from protocol --gave values on 
different days than what they were suppose to.  If you ca n include this data and with that 
data you can prove that women were able to follow the protocol, then you can comment 
on feasibility.  However, with only 156 pairs of hCG values, it seems as though you have 
a great deal of missing hCG values and therefore , it is UNFEASIBLE to use the SQPT in 
this current protocol.  
 
 
 
Methods:  
 
1.) Don't call this two studies as I'm then looking for two sets of methods.  One study, two 
study sites  
 
2.) The timing of the SQPT and serum hCG testing, u/s timing, and f/u timing sho uld be 
more clear here.  You should also state what you measured with your interview better --
what was the actual outcome?  I have no real understanding of your methods based on 
this abstract.  
 
 
 
Results:  
 
1.) You do list stats in your abstract that aren't in your paper (granted it's not too hard to go 
from what you have the manuscript to the abstract).  In general, this is not a good 
practice.  
 
 
2.) The outcome of interest (matched vs. discordant pairs) is not well defined.  Your 
background never demonstrates wh y that should be an outcome of interest.  Why is this 
outcome even important?  
 
 
 
Conclusion:  
 
1.) the first sentence in your conclusion is fine.  Your second sentence is not supported in 
any way by your study and severely over -reaches your data.  You should remove this 
sentence and allow more words to clarify your methods or improve your results --the two 
sections of the abstract that are weak but really should be the meat of the abstract.  
 
 
 
Introduction  
 
1.) Your first paragraph is like an intro to your intro.   It is weird to introduce the 
MLPT/SQPT here and then to go into it in detail in the third paragraph too.  I would 
recommend getting rid of your first paragraph and just starting your intro with your 
second paragraph.  
 
 
2.) As above pick SQPT or MLPT.  If y ou are going to use MLPT, explain why you need to 
change the language that is making you inconsistent with prior literature.  
 
 
3.) You use the term "tool" throughout your manuscript and it means different things 
depending on where you use it.  I would strong ly recommend getting rid of the word 
"tool" when you write and use terms that are more specific and elegant.  In line 14, for 
example, change to "utility as an instrument to assess" instead of "utility as a tool in 
assessing."   In page 4 line 55, change " tools" to something like "monitoring tests" and 
page 4 line 58 change tool to "modality" vs. "test"  
 
 
4.) Sentence on page 4, Line 12 -14 that describes prior literature (other lines below that 
pertain to the same literature): Is this test used in clinical pr actice at all or just in the 
research setting?  You will want to provide if this is just a research test or not, especially 
if you are trying to make the point that SQPT will impact clinical practice for ART.  
Provide literature to demonstrate that SQPT ha s affected clinical practice for Med AB as 
it affects the relevance of your study.  Your next sentence states that this test will affect 
REI practice but you can't jump to that if you are just talking about the research setting 
for Med AB.  If you remove t his paragraph, as I recommend, you should then add a 
comment about clinical practice to the paragraph on MLPT on page 5.  
 
 
5.) Page 4 Line 55: Remove  "possibly improve quality."  This is in no way supported by 
anything in your study, and all reference to th is needs to be removed from your 
manuscript.  
 
 
6.) Page 5 Line 4: "establishment of early pregnancy" should be changed to "early ART 
outcomes" because this is a more broad term and you want to be able to comment on 
established pg's and non -pregnancy.  
 
 
7.) Page 5 Line 4 should be changed to "The test can be performed serially to ascertain 
initial presence of the pregnancy hormone hCG to monitor sequential hCG levels..." 
again, to be more inclusive of pg outcomes (rise or fall)  
 
 
8.) Page 5 Line 11: an MLPT  should be a MLPT  
 
 
9.) Page 5, Line 9 -21 should be removed altogether r as you have absolutely no data to back 
up this hypothesis with regards to quality.  If you want to comment on how your data 
may fit into larger clinical practice/other existing literature , you can do this in the 
discussion.  But the intro is not the place that allows for you to pontificate.   
 
 
10.) Page 5, Line 48: You need to remove that this is a test about feasibility from your 
hypothesis paragraph.  You do not give any results that supp ort that you studied 
feasibility, in fact, quite the opposite since your data actually indicates (from protocol 
changes and number of hCG pairs) that women were actually not very good about 
knowing how to or following through with the use of this test  
 
11.) In the intro you need to set up the data you are planning to study and why.  You need to 
show that this was a prospective study that was planned deliberately.   you really should 
describe what you meant a priori to study.  Why would you study nothing more  than 
concordance of rising/falling SQPT vs. serum hCG tests?  What is the precedence for 
studying this and what does concordance even mean?  You have semi -quantitative data 
and quantitative data.  Why are you just studying the binary rise/fall concordance  and not 
the concordance of actual values?  Otherwise, it seems more like you got data and then 
planned the study after the data was collected (retrospective) or that the results didn't 
give you what you wanted (concordance between semi -quantitative and qu antitative 
values) so you decided to change your outcome to this non -specific/no clear meaning 
binary concordance.  I'm going to assume the prior SQPT data from Med AB studies 
looked at actual values of semi -quantitative results and compared to quantitativ e results.  
This should be the standard and your reader expects to be told this information.  
 
 
12.) Why Vietnam?  What is it about this population that prompted you to study it and why 
might results and conclusions be different between your US and your Vietn am cohort?  
 
 
 
 
Methods:  
 
1.) This is one study with two study sites.  Change your language to reflect this since you 
don't give methods and results from two studies.   
 
 
2.) Avoid passive voice in Page 6 line 16  
 
 
3.) Was there any language requirement in Vietnam?   It's probably not an issue there, but it 
should at least be stated since you bring it up for the California cohort  
 
 
4.) Page 7, line 6: What do you mean you "interviewed" participants?  Be more specific 
about your methods of interview and what you asked t hem and why.  Was this a written 
or electronic survey? was this a face -to-face interview?  How long did it take?  what were 
the number of items and the specific questions that were asked with regards to content?  
Open or closed ended?  Validity of the ques tions?  All of tables, figures, conclusions 
hinge on this data so you need to be much more specific and detailed about the data you 
collected and why.  
 
 
5.) Page 7, line 6: NONE of the results you give actually pertain to feasibility, including 
nothing about  women's "perceptions about feasibility" (what is that anyway??).  All of 
your questions pertain to satisfaction and just a touch on convenience.  Do not over 
extend what you can get from your data.  
 
 
6.) you really should describe what you meant a priori to  study.  Why would you study 
nothing more than concordance of rising/falling SQPT vs. serum hCG tests?  What is the 
precedence for studying this and what does concordance even mean?  You have semi -
quantitative data and quantitative data.  Why are you just studying the binary rise/fall 
concordance and not the concordance of actual values?  
 
 
7.) you say you did analyses but what analyses did you actually do?  Seems all descriptive by 
your results, but you at least need to describe you analysis plan  
 
 
 
Results:  
 
1.) Page 9, Line 26: The pg women in Vietnam who dropped out --she didn't drop out 
because she had a threatened AB, she dropped out because she deviated from study 
protocol or she was lost to f/u or something else.  If she dropped out due to threatened 
AB the n you need to explain why threatened AB would lead to exclusion from continuing 
the study.  But I don't think you mean that to be the case.  I.e. be more scientifically 
specific about why this woman did not continue to give you data  
 
 
2.) Page 9, paragraph 2 : you need to explain the completeness of your data to put your data 
into context.  How much missing data did you have?  How much SQPT was collected on 
the days they were supposed to be collected and how many women collected there data 
on different days an d how many days difference between SQPT and serum did you give 
to still count this as a "pair."  This is especially true if you are trying to make any 
comment about feasibility.  Your results need to be described more thoroughly, more 
systematically.   
 
 
3.) 156 pairs?  That seems like a lot of missing data (42 pregnancies x 6 bHCG collections 
per pregnancy + 60+ women who did not have a pregnancy who should have also given 
you bHCG pairs.  You have <50% of the data that would be expected.)  This seems like 
this protocol is actually NOT feasible.  You then need to comment in the discussion about 
all of your missing data.  
 
 
4.) As above, why study nothing more than concordance of rising/falling SQPT vs. serum 
hCG tests?  What is the precedence for studying this a nd what does concordance even 
mean?  You need to give these results, otherwise, it makes it look like you are hiding lack 
of concordance between semi -Q and Q data.  Or that there is so little actual pairing 
between the two (such a long time between the col lection of the two values) that 
demonstrate the true lack of feasibility of women following through with this self -
monitored data collection.  
 
 
5.) Avoid the overlap of your text and figures.  You don't need to have the data repeated in 
both.  You should def initely remove Table 2 because it just repeats what you say in your 
text.  Most of Table 3 is an overlap as well.  What I'd recommend is that you simplify 
your results section that pertains to data that is in Table 3 (to avoid repetition) and that 
you add statistics that compare US to Vietnam populations (as you have them separated 
in Table 3).  There is every reason to think that US and Vietnam women are different 
with regards to what they find acceptable, convenient, and feasible.  If they do or don't 
depending on your data, it needs to be identified in your results and commented on in 
your discussion.  
 
 
 
 
Discussion:  
 
In general, really needs to be completely reworked to be clearer, not an over -reach of your data, 
and actually do the job of what a discussion is supposed to do (paragraph 1: summarize your 
data, paragraph 2: discuss your findings in the larger context, paragraph 3: strengths and limits of 
your study/data, paragraph 4: larger implications of your study/data).  
 
 
Page 11, lines 14 -39.  You have absol utely nothing to back up a comment about quality of care.  
In fact, your data makes a claim for the opposite.  Please do not over reach when putting your 
study in context of other work or implications.  
 
 
Page 12, paragraph 2: these protocol violations prove against feasibility.  You really need to 
avoid making a positive comment about feasibility and actually address the lack of feasibility.  
 
 
Page 12, last paragraph, did your senior authors read this?  PB is the main scientists who has any 
data on the MLPT/SQP T.  This whole paragraph really needs to be re -worked.  What is your 
message?  What are you trying to say?  
 
 
Page 13, paragraph 1: overreaches your data  
 
page 13, paragraph 2: needs to be removed altogether  
 
Figure 1: Be consistent in calling this a SQPT vs. MLPT.  If the device calls itself a SQPT and 
the prior data calls this a SQPT, you need to explain why you think MLPT is the better name.   
Are the methods 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 conclusions 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 manuscript o r would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written Englis h 
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, fees, funding,  or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
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 interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no  competing interests below.  
 
I agree to the open peer review policy of the journal. I understand 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 a n Open Acces s 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 included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal