P-474 State-Trait Anxiety Inventory (STAI) punctuations as a non-invasive method for evaluating endometrial prognosis associated with cortisol and estradiol endometrial levels in IVF patients
Authors: Martí-Garcia D , Dolz P , Sebastian-Leon P , Devesa-Peiro A , Vidal C , Pérez E , Meseguer M , Dura E , Diaz-Gimeno P 
Published: July 2024

Abstract

Study question
Are STAI State punctuations a potential non-invasive marker of endometrial prognosis in IVF patients?

Summary answer
Being stressed (determined by STAI State punctuations) is positively and negatively correlated with endometrial cortisol and estradiol levels, respectively, and highly associated with pregnancy consecution.

What is known already
Despite it is well known IVF treatments are a source of stress, this factor is frequently overlooked mainly due to the difficulty of stress evaluation and the lack of accurate biomarkers, not being standardized in the clinical setting. Steroid hormones are essential for reproductive physiology and highly related to well-known stress biomarkers such as cortisol. The lack of correlation between endometrial and serum steroid levels creates the need to look for non-invasive tools reflecting the endometrial microenvironment. In this study, by molecularly and psychologically characterizing patients, we aim to unveil non-invasive potential markers of stress associated to pregnancy consecution.

Study design, size, duration
This prospective cohort study included a total of 74 IVF patients (&lt;45 years old, no uterine or systemic pathologies and good quality embryos) who underwent endometrial biopsy collection in mid-secretory phase for metabolites measurement between 2019 and 2023. These patients also underwent psychological evaluation by stress related questionnaires.

Participants/materials, setting, methods
The endometrial concentration of eleven steroid metabolites was measured by ultra-performance liquid chromatography-tandem mass spectrometry. Patients also underwent stress and anxiety evaluation (STAI), and reproductive outcomes in the first embryo transfer after biopsy collection were followed up. Wilcoxon and Barnard’s test were applied to compare the mean and proportion of stressed/unstressed, pregnant/not pregnant patients and metabolites levels. Correlations between metabolites’ levels and the proportion of stressed patients were evaluated by Pearson’s correlation coefficient.

Main results and the role of chance
Patients with STAI State punctuations &gt; 60 presented higher mean endometrial cortisol levels (8.01 ng/g (n = 23) vs 5.08 ng/g (n = 35), p-value = 0.05) and lower mean estrone levels (54.97 ng/g (n = 23) vs 56.31 ng/g (n = 35), p-value = 0.049) than those patients with STAI State punctuations &lt; 60. Also, in patients with high endometrial estradiol levels (&gt;2 ng/g) a higher significant proportion of unstressed patients (STAI State &lt; 60) was observed (88.9% vs 52% of unstressed patients in &gt; 2 ng/g and &lt; =2 ng/g estradiol concentrations, respectively) (n = 34, p-value = 0.036). As expected, a significant positive correlation between endometrial cortisol levels and stress (measured by STAI State questionnaire) (cor = 0.977, p-value = 0.023) and a negative correlation between endometrial estradiol levels and stress (cor = -0.9945, p-value = 0.0055) was evidenced. Additionally, a higher proportion of pregnant patients was observed when endometrial estradiol concentrations were high (&gt;1 ng/g) (78.9% vs 50% pregnant in &gt; 1 ng/g vs &lt; =1 ng/g estradiol respectively, p-value = 0.035) and a higher proportion of not pregnant patients was observed when endometrial cortisol concentrations were high ( &gt; =13.9 ng/g) (80% vs 34.4% not pregnant in &gt; =13.9 ng/g and &lt;13.9 ng/g cortisol respectively, p-value = 0.029).

Limitations, reasons for caution
Although we have employed validated psychological questionnaires and stress biomarkers, a causal relationship between stress and reproductive outcomes should be further explored.

Wider implications of the findings
This study demonstrated a significant correlation between stress and cortisol and estradiol levels. Since both metabolites’ levels were also related to pregnancy chances, STAI State psychological evaluation could be implemented in the clinical practice as a non-invasive method to prevent endometrial failure through psychological counseling.

Trial registration number
Not applicable