Reviewer’s report
Title: 
Combination of pioglitazone and clomiphene citrate versus clomiphene
citrate alone for infertile women with the polycystic ovarian syndrome
Version: 
0 
Date: 
13 Feb 2021
Reviewer's report:
English should be revised. 
Methodology: As authors state in their background, there are two profiles within
PCOS patients. Those with and those without hyperinsulinemia and insulin
resistance. Moreover, as they also state "abnormal glucose metabolism may
significantly improve with weight loss; weight loss may reduce
hyperandrogenism and reinstate ovulation function" and as it has already been
proven that "Treatment of insulin resistance might induce ovulation, especially in
obese women who have higher degrees of insulin resistance". Therefore, these
aspects (insulin resistance AND obesity) should have been controlled in this
study otherwise these factors would act as confounding factors.
Patients selection: "Inclusion criteria were infertile women aged 18-38 years who
had PCOS with routine hysteroscopy". I do not understand what authors want to
mean by "PCOS with routine hysteroscopy"??? 
Then they state that "The diagnosis of the polycystic ovarian syndrome is based
on the AES criteria" but no limits are clarified for this study, f.e. how was
hirsutism defined or other hyperandrogenic symptoms?
Intervention: The sentences "The second phase of treatment was started in cases
with a menstrual period. Moreover, 150 mg clomiphene citrate was administered
again" are unclear to me. Was this second treatment only with clomiphene citrate
or also with pioglitazone and placebo? Were the results of this second treatment
included in the analysis? Also, how many patients in each group needed
Medroxyprogesterone acetate to induce a mature follicle? This late fact may also
act as confounder. 
Sample size calculation: As authors state, "The sample size was calculated using
PASS 11 software and from the formula of comparing the average number of
follicles in each group" thus, even if there had been differences in pregnancy
rate, they would have never been found since the sample is too low to allow
showing differences on that. 
Discussion: Authors mention "in our study fertilized oocytes were not differed
statistically significant in two groups". How do authors know? Since this is a IUI
study (not IVF) there´s no way to know the number of fertilized oocytes!
Conclusion: "However we are obviously in the new era of recognition and
treatment of women with PCOS. In the past, we were effectively treating the
specific problems of infertility, bleeding due to uterine dysfunction, and
hirsutism. Now we have the opportunity (and indeed the duty) to provide
interventions that can prevent or rectify some of infertility's metabolic
complications (which have a significant impact on overall health and quality and
quantity of life)". This might be a comment to be included in discussion but not
a conclusion of this work, especially since not a single metabolic result has been
monitored. 
References: Style should be homogeneous. 
Table 2: Please define "medium" and "large" follicles. 
Table 3: How was "amount of ovulation per cycle" calculated? Percentage of
large follicles/total medium+large follicles? Percentage of patients that received
HCG/total of patients under stimulation?
Figure: When describing enrolment you mention exclusion 32 and not meeting
criteria 19. Which is the difference between both? Please clarify. 
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Is the study design appropriate to answer the research question (including the use
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presented?
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