Reviewer’s report
Title: 
Falsely elevated serum estradiol in woman of reproductive age led to
unnecessary intervention and delayed fertility opportunity: a case report and
literature review
Version: 
0 
Date: 
06 Jan 2022
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
RELEVANCE - Does this case report make a contribution to medical
knowledge, have educational value, or highlight the need for a change in clinical
practice or diagnostic/prognostic approaches? 
Yes, this report contributes to medical knowledge
CASE DESCRIPTION - Are the details of the case sufficiently well described to
understand the patient's symptoms and course of treatment? 
Yes, the description of the case is sufficient
DIAGNOSIS/INTERPRETATION - Based on the facts presented, are the
diagnosis, interpretation, and course of treatment medically sound?
Yes, the work described is medically sound
DISCUSSION OF THE CASE - Does the discussion appropriately analyse the
importance of the findings and their relevance to future understanding of disease
processes, diagnosis or treatment? Has an adequate literature review pertinent to
the case been included?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Could an appropriately REVISED
version of this work represent a technically sound contribution?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: I read carefully this case report, which tries to shed
light on an important and underrated topic. Overall, language revision appears
mandatory to improve the paper, as well as to incorporate some additional
elements of paramount importance to the discussion. For these reason, I
recommend minor revisions.
REQUESTED REVISIONS: 
I would recommend to take into account the following suggestions:
- the whole manuscript needs extensive language editing by a native speaker, in
order to improve grammar and style.
- To date many efforts are spent to identify a correct algorithm which considers
woman's age and ovarian reserve markers as a tool to optimize reproductive
outcomes (with or without IVF). Nevertheless, current available evidence
regarding PCOS women, particularly the ones with high AMH, does not seem
adequate. I would be glad if the authors discuss this important point, referring to:
PMID: 30242498; PMID: 32613875.
- Accumulating evidence suggests that one of the most important mechanisms of
PCOS pathogenesis is the insulin-resistance. For this reason, the use of insulin-
sensitizers, such as inositol isoforms, gained increasing attention due to their
safety profile and effectiveness. Authors may better discuss this point, taking to
account these points (PMID: 26927948).
- The case described in this article presents 
a combination of PCOS, Hashimoto's thyroiditis and subclinical hypothyroidism.
In this scenario, recent pieces of evidence suggested that among
phosphoinositides, phosphatidylinositol 4,5- bisphosphate (PIP2) is the precursor
of inositol triphosphates (IP3), second messenger of several hormones including
thyroid-stimulating hormone (TSH). As a second messenger in the
phospholipase C (PLC)-dependent inositol phosphate Ca2+/DAG pathway, Myo-
Inositol is essential to produce H2O2 required for the synthesis of thyroid
hormones. Consequently, depletion of Myo-Inositol or impaired inositol
dependent TSH signaling pathway may predispose to the development of some
thyroid diseases, such as hypothyroidism. I would stress, at least briefly, this
important endocrine cross-talk, referring to: PMID: 34040582.
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