Title: The relationship between serum progesterone level on the day of HCG trigger in IVF/
ICSI cycles and oocyte maturation and embryo quality: A retrospective observational study
Version: 2 Date: 13 Nov 2024
Reviewer:  Yuquan Chen
Reviewer's report:
The manuscript "The Relationship Between Serum Progesterone Level on the Day of HCG
Trigger in IVF/ICSI Cycles and Oocyte Maturation and Embryo Quality" investigates an
important topic in reproductive medicine and provides potentially valuable insights into the
relationship between serum progesterone levels and IVF outcomes. While the study is relevant
and addresses a clinical challenge, several substantive issues require attention to enhance
its scientific rigor and practical applicability. The statistical methodology, while including t-
tests, chi-square tests, and regression analysis, lacks sufficient justification for the choice of
these methods, particularly given the heterogeneity in progesterone levels and the presence of
confounding variables such as BMI, age, and gonadotropin dosage. The authors should provide
a more detailed explanation of the analytical framework and consider employing multivariate
techniques to account for potential confounders in a single comprehensive model.
The determination of the progesterone cutoff level at 1.54 ng/ml, a central finding of the
study, is inadequately explained. The chart provided does not convey the statistical rigor behind
this conclusion, and the manuscript does not describe whether methods such as ROC analysis
were employed. A more robust statistical approach to determine this threshold is necessary to
substantiate its clinical relevance. Furthermore, while the study focuses on short-term outcomes
such as oocyte maturation and embryo quality, it fails to address long-term outcomes like live
birth rates or miscarriage rates. The authors acknowledge this limitation but do not provide
sufficient discussion on how these findings could inform clinical practice or patient counseling
in IVF.
The discussion on the clinical implications of the identified cutoff is limited, as the manuscript
does not offer practical guidance for managing progesterone levels during ovarian stimulation.
Specific recommendations for adjustments in stimulation protocols or monitoring strategies
would make the findings more actionable for clinicians. Additionally, the manuscript contains
some redundancy between the "Materials and Methods" and "Results" sections, particularly in
descriptions of statistical methods and study design, which could be streamlined to improve
readability and conciseness. The exploration of the mechanisms underlying progesterone’s
effects on oocyte and embryo quality is also underdeveloped. While the manuscript touches upon
granulosa cell sensitivity and endometrial receptivity, it does not link these concepts directly to
its findings or provide sufficient references to support these discussions.
The single chart included in the manuscript does not effectively convey the key findings, and
its format is unclear. Enhancing the data visualization by incorporating ROC curves for cutoff
determination, scatterplots illustrating correlations, and regression result visualizations would
improve the manuscript's clarity and impact. Overall, the study presents relevant findings but
requires significant revisions to address these methodological, interpretative, and structural
issues. A more detailed and systematic approach to analyzing and presenting the data, along
with a stronger focus on clinical implications, is crucial for improving the manuscript's quality
and utility in the field of reproductive medicine.