Title: Impact of Preconceptional Serum Thyroid Stimulating Hormone Values Ranging
Between 2.5 and 4.5 mIU/L on Live Birth Rates Following Ovulation Induction and Intrauterine
Insemination Treatment for Unexplained Infertility
Version: 1 Date: 21 Feb 2021
Reviewer's report:
Dear Authors,
This retrospective cohort study aims to answer if women with TSH levels <2.5 mIU/L and
those with 2.5 – 4.5 mIU/L have different live birth rates following ovulation induction and
intrauterine insemination (OI+IUI) treatment for unexplained infertility. The authors report
similar live birth rates between the groups.
This is a clinically relevant study as many clinicians face a dilemma whether to start thyroid
medications when women undergoing fertility treatments are found to have TSH levels between
2.5 – 4.5 mIU/L. Different guidelines and studies offer different approaches, complicating the
issue. Thus, this study would be of use. Moreover, since OI+IUI is an underrepresented area in
medical literature overall, it may fill a gap.
Here are my major and minor suggestions for improvement.
Major Points:
The title can be improved if written as ‘’Does Thyroid Stimulating Hormone Values Between
2.5 And 4.5 Miu/L Affect Live Birth Rates In Women Undergoing Ovulation Induction
And Intrauterine Insemination Treatment For Unexplained Infertility?’’ or ‘’Impact Of
Preconceptional Serum Thyroid Stimulating Hormone Values Between 2.5 And 4.5 Miu/L On
Live Birth Rates Following Ovulation Induction And Intrauterine Insemination Treatment For
Unexplained Infertility ‘’
The methodology and results are clearly defined. Results are concise but clear, no unnecessary
repetition of outcomes that are already represented in the Tables.
A very important but unaddressed issue is the timing of the TSH testing before the treatment. The
authors should clearly state their common practice (When they screen for TSH? Right before
treatment? During investigating for infertility? There can be a long lag, if latter is the case). They
should also state what is the maximum interval between TSH testing and start of the interval.
TSH cut-off value is written as ‘’0.27’’ in line 115 and and as ‘’0.3’’ in line 141. The authors
should correct it.
In live birth definition in the ‘’outcome measures’’ section, using a more objective expression
such as ‘’ positive heartbeat’’ can be better than ‘’ evidence of life’’, which is somewhat vague.
Anti-TPO have not been screened for women in the study. It would be good if the authors could
provide them, even for some, if not all patients, if they have access to this information. If they do
not, it can remain as it is, since the authors list this as a weakness of the study in the discussion
section anyway.
Sample size is large and the endpoint is the ultimate endpoint in infertility studies, live birth.
This strengthens the study.
Minor Points:
P values can be given with 2 digits after decimal point, instead of three.
‘’fT4’’ levels should be written in full in line 61, and abbreviated in line 114 instead.
The sentence ending with ‘’… recommended.’’ Requires a reference. I believe the authors refer
to reference number 10.
Line 116: the word ‘’previous’’ is redundant.
Line 159: the word ‘’period’’ is redundant, ‘’2-3 days’’ alone is sufficient.
In my opinion, due to its relevant study question, large size, strong endpoint (live birth), this
paper may be suitable for publication after some minor revisions and improvements.
After the revisions made , the article can be accepted.
Sincerely