Title: Number of vaginal lactobacilli in postmenopausal women with vaginal atrophy before
and after treatment with erbium YAG laser, a randomized sham-controlled trial
Version: 5 Date: 07 Mar 2023
Reviewer's report:
"PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
No - there are major issues
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
No - there are major issues
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
No - there are major issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Maybe - with major revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: I read carefully the manuscript ""Number of vaginal lactobacilli in
postmenopausal women with vaginal atrophy before and after treatment with erbium YAG laser,
a randomized sham-controlled trial"". The authors' efforts are clear, but the study suffers from
a significant amount of biases and several points need to be clarified by the authors (especially
about methodology).
REQUESTED REVISIONS:
I recommend to take into account the following suggestions:
- The article needs extensive language editing by a native speaker, in order to improve grammar
and style.
- Introduction: authors should add further details to discuss non-hormonal strategies for
vulvovaginal atrophy (for comprehensive summary of available evidence, they may refer to:
PMID: 34703415).
- Methods: who kept the randomization schedule?
- Methods: the authors should have used objective and validated methods to assess pre- and
post-treatment outcomes, such as the Vaginal Health Index Score (VHIS). VAS score to assess
vaginal atrophy is not accurate enough, so this is a significant bias of the study.
- Methods: the authors declared they have included women older than 40 years. This allowed,
clearly, the inclusion of both pre-menopausal and post-menopausal women, and so represents
another significant bias which do not allow a proper data interpretation.
- Methods: did the authors include women with a previous cancer? If yes, which type? It
would particularly important to give information about this point, since many women previous
diagnosis of hormonal-dependent cancers (such as breast and endometrial cancers) are reluctant
to use hormonal vaginal therapies, so Er:YAG laser may be the preferred option (selection bias);
in addition, women with previous radiotherapy may develop vaginal stenosis, and this should
be considered another potential bias.
- Methods: was the study advertised?
- Methods: Did the authors give reimbursement for patients to be enrolled or continue the study?
- Methods: the authors should clearly declare what they considered primary and secondary
outcomes.
- Methods: did the authors include sexually active women? This should be clearly defined. In
case they have included sexually active women, Female Sexual Function Index should have
been used to investigate also this element.
- Methods: the pilot study used for sample size calculation must be referenced, and this
calculation must be based on the primary outcome of this pilot study; conversely, this raisej
serious concerns and the study may be considered not powered enough to detect small
differences between the two groups (indeed, the improvement in the lactobacilli grading did not
reach statistical significance: adjusted OR = 5.32, 95%CI = 0.5-56.21).
- Methods: did the authors exclude other gynecological and non-gynecological diseases? This is
of paramount importance, since 54.5% of the patients reported dyspareunia: are the authors sure
that they are not affected by endometriosis/adenomyosis? Did they rule out these conditions? If
endometriosis/adenomyosis were note excluded, this may represent a bias, considering that these
conditions are associated with specific microbiome alterations (for a quick overview: PMID:
33851803).
- Discussion: since the study was performed in single-blind, i.e., the doctor who evaluated the
results of the treatment was aware of the allocation of each patient, this representj a very serious
bias of the investigation."