Authors' Response to the Commentary on “Micronized Vaginal Progesterone Dose and Serum Progesterone Thresholds Determine Reproductive Outcomes in Frozen–Thawed Embryo Transfer With Hormone Replacement Therapy”
Ayumu Ito, Mami Sekiguchi, Yukiko KatagiriABSTRACT
Background
This response addresses the methodological concerns raised in a commentary on our study evaluating vaginal progesterone dose, serum progesterone concentrations, and reproductive outcomes in hormone replacement therapy–frozen embryo transfer cycles.
Methods
We revisited the study objectives, analytical approach, interpretation of the proposed serum progesterone threshold, formulation‐specific considerations, treatment‐selection practices, and the potential influence of insurance reform.
Main Findings
We clarify that the proposed serum progesterone threshold should not be interpreted as a definitive clinical cutoff and that differences among progesterone formulations and non‐random treatment selection may have influenced the observed associations. We also emphasize that several concerns raised in the commentary, including residual confounding and limitations inherent to the retrospective observational design, were acknowledged in the original manuscript.
Conclusion
Our findings should be interpreted as exploratory observational associations rather than causal estimates. They may help generate hypotheses and inform the design of future prospective studies evaluating progesterone regimens and serum progesterone monitoring in hormone replacement therapy–frozen embryo transfer cycles.