Title: Plasminogen Activator Inhibitor 1 is a novel predictor in human serum / follicular fluid
for diminished ovarian reserve
Version: 1 Date: 06 May 2024
Reviewer's report:
This is a case control study analyzing the serum and follicular PAI-1 concentration in infertile
patients with or without decreased ovarian reserve (DOR). The results showed that the
expression of serum and follicular PAI-1 were significantly higher in the infertile DOR patients
than the patients without DOR. The authors did the correlation analysis and concluded that “PAI
1 is expected to become a marker for predicting and diagnosing of DOR.” Author the idea would
be interesting, the interpretation of the study results is flawed and sometimes overinterpreted.
And the main conclusion cannot be supported by the results. This is a cross-sectional study
which can only showed correlation. The predictability of serum PAI-1 concentration in the
development of DOR cannot be confirmed in this study design. Moreover, DOR can be directly
defined by serum AMH test, the value of measuring PAI-1 expression for the diagnosis of DOR
is questionable. It would be more valuable to dig into the pathophysiology of how PAI-1 in
involved in DOR and to figure out possible novel treatment strategy.
Abstract
The study population is “infertile” woman and this important information is not revealed in the
abstract.
It would be better to define more clearly what is the known role of PAI-1 in ovarian function.
“Plasminogen activator inhibitor 1(PAI 1) makes a difference to ovarian function.” This
sentences is kind of rough.
“ROC indicated that serum PAI 1 has great prediction of DOR.” The predictability, sensitivity,
specificity of the ROC should be mentioned here.
Background
The known physiological roles of PAI-1 and related signaling pathways are not adequately
introduced in the introduction section.
One important reference which is published in Fertility and Sterility is missing. (PMID:
24355042)
Material and Method
Did the diagnosis of DOR in this study need to fulfill all three items, FSH, AMH and AFC?
What is the infertility causes in the DOR and control group in this study?
Were the PCOS patients and endometriosis patients included in this study?
“Clinical pregnancy was defined as a pregnancy diagnosed by ultrasonographic visualization of
one or more gestational sacs or definitive clinical signs of pregnancy.” What are definite clinical
signs of pregnancy here?
Cyclophosphamide is not the active form in vitro. It would be better to utilize the metabolites
of cyclophosphamide in the in vitro experiments.
Statistics: Please provide standard deviation instead of standard error for the continuous
measurements.
Results
Is there an explanation for such a high miscarriage rate in this study? 61.1% vs 28.6%? Which
one is DOR group and which is control? This is a lot higher than the reported miscarriage rate
in the literatures.
There is significant difference in the ovarian stimulation protocols between the DOR and control
group, that the former group had more antagonist protocol and the latter group had more Long
protocol. The degree of ovarian suppression and the pharmacological effects between Long and
antagonist protocols are known to be different. Please provide reasonable explanation for the
possible confounding factors.
What is sequential treatment in Table 2?
Why seven ongoing pregnancies followed by 9 live births?s
Discussion
“Our results are consistent with the previous findings that PAI 1 levels were higher in ovarian
dysfunction related polycystic ovary syndrome (PCOS). “
PCOS and DOR are totally different disease entities.
“Therefore, our finding suggests that the increase of PAI 1 may raise the risk of pregnancy
failure in IV F ET women by reducing endometrial thickness. “
This sentence is too speculative and cannot be supported by the study results at all. The causes
of pregnancy failure are too simplified.