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Endometrial cortisol level and its relationship with psychological stress, molecular tissue changes, and clinical outcomes in infertile women
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  • Published: 24 February 2026

Endometrial cortisol level and its relationship with psychological stress, molecular tissue changes, and clinical outcomes in infertile women

  • Diana Marti-Garcia1 na1,
  • Patricia Sebastian-Leon1 na1,
  • Pilar Dolz del Castellar2,
  • Almudena Devesa-Peiro1,
  • María del Carmen Vidal2,
  • Laura Caracena2,
  • Francisco José Sanz1,
  • Rebeca Esteve-Moreno1,3,
  • Estrella Dura-Ferrandis4 &
  • …
  • Patricia Diaz-Gimeno1 

Scientific Reports , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Biomarkers
  • Diseases
  • Endocrinology
  • Genetics
  • Medical research

Abstract

Despite fertility treatments are a stressful journey, there remains a lack of studies assessing how stress is affecting endometrial function in infertility. This prospective cohort study, including 84 endometrial biopsies, aims to elucidate the effect of stress, measured by different approaches, in the endometrial function in In Vitro Fertilization treatments. This population was molecularly characterized by measuring endometrial cortisol levels and endometrial transcriptomic profiles, and psychological aspects measured by the State-Trait Anxiety Inventory test. A relationship between endometrial cortisol levels and psychological stress punctuation was found. Psychologically stressed patients had increased endometrial cortisol levels (5.4 ng/g vs. 3.45 ng/g; p = 0.05, in the limit of significance) and cortisol levels correlated with psychological test punctuations (cor = 0.97, p < 0.05). From the clinical point of view, patients with cortisol levels ≥ 13.9 ng/g had a 32% relative higher risk of not becoming pregnant (p = 0.003). Molecular evidences showed, increased cortisol levels were significantly associated with changes in 182 genes in endometrium (p < 0.001) and psychological stress scores were significantly associated with changes in 12 genes involved in key functions for embryo implantation and development (p < 0.001). Psychological evaluation could serve as a less-invasive screening tool to identify at-risk infertility patients and implement preventive psychological interventions in the clinical setting.

Data availability

Some of the findings reported in this scientific article were presented at the 39th Annual Meeting of European Society of Human Reproduction and Embryology held in Copenhagen, Denmark, June 25–28, 2023; and at the 40th Annual Meeting of European Society of Human Reproduction and Embryology held in Amsterdam, Netherlands, July 8–10, 2024. Data including STAI results and metabolic concentrations will be made available to the editors of the journal for review, upon request, should there be any queries. The RNA-seq dataset generated and analysed during the current study are available in the Gene expression omnibus (GEO) repository, [GSE310309].

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Acknowledgements

The authors thank the Analytic Unit and the Genomics Unit of the Instituto de Investigación Sanitaria La Fe (Valencia, Spain), especially to Marina Lopez-Nogueroles and Cristina Cardona-Gay; the patients who participated in the study, and the clinical staff who contributed to participant recruitment and organization at IVI Valencia. We also thank Professor Peter Rogers and Dr Jaqueline Donoghue from the University of Melbourne for generously providing the endometrial cell line. The authors especially thank Eva Pérez for helping with patient psychological evaluations and April Gocha for her editorial services in preparing the manuscript for publication.

Funding

This research was funded by IVI Foundation (1805-FIVI-033-PD), Centro para el Desarrollo Tecnológico y la Innovación (CDTI) (IDI20210289) and Instituto de Salud Carlos III (ISCIII, Spanish Ministry of Science and Innovation) co-funded by the European Regional Development Fund ‘A way to make Europe’ (PI23/00806[P.D.-G.]). P.D.-G. was supported by the Instituto de Salud Carlos III (Spanish Ministry of Science and Innovation) through the Miguel Servet programme (CP20/00118) co-founded by the European Union. D.M.-G. was supported by the Spanish Ministry of Science, Innovation and Universities (FPU/19/03247). P.S.-L. and F.J.S. were funded by the Instituto de Salud Carlos III through the Sara Borrell programme (CD21/0132 and CD23/00032, respectively) co-founded by the European Union. R.E.-M. was funded by CIACIF grant programme (CIACIF/2022/447) of Ministry of Innovation, Universities, Science and Digital Society, Generalitat Valenciana, Spain.

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Author notes

  1. These authors jointly supervised this work: Diana Marti-Garcia and Patricia Sebastian-Leon.

Authors and Affiliations

  1. IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Av. Fernando Abril Martorell 106, Torre A, Planta 1ª, Valencia, 46026, Spain

    Diana Marti-Garcia, Patricia Sebastian-Leon, Almudena Devesa-Peiro, Francisco José Sanz, Rebeca Esteve-Moreno & Patricia Diaz-Gimeno

  2. IVIRMA Global Research Alliance, IVI RMA Valencia, Plaza de la Policía Local nº 3, Valencia, 46015, Spain

    Pilar Dolz del Castellar, María del Carmen Vidal & Laura Caracena

  3. Department of Paediatrics, Obstetrics, and Gynaecology, University of Valencia, Av. Blasco Ibáñez 15, Valencia, 46010, Spain

    Rebeca Esteve-Moreno

  4. Instituto de Investigación en Políticas de Bienestar Social -Polibienestar, University of Valencia, C/del Serpis, 29, Algirós, Valencia, 46022, Spain

    Estrella Dura-Ferrandis

Authors
  1. Diana Marti-Garcia
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Contributions

D.M.-G.: Investigation (participant recruitment, clinical follow-up, sample pre-processing, RNA extraction, sequencing), formal analysis, validation (cell culture and RT-qPCR), visualization, writing – original draft. P.S.-L.: Conceptualization, formal analysis, writing – review & editing. P.D.: Conceptualization, investigation (psychological evaluation, participant recruitment). A.D.-P.: Conceptualization, investigation (participant recruitment). M.C.V.: Conceptualization, investigation (participant recruitment, biopsy collection) and funding acquisition. L.C.: Investigation (participant recruitment). F.J.S.: Validation (cell culture). R.E.-M.: Validation (cell culture). E.D.-F.: Conceptualization, methodology, supervision. P.D.-G.: Conceptualization, methodology, formal analysis, writing – original draft, writing – review & editing, supervision, project administration, funding acquisition. All authors read and approved the final version of the manuscript.

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Correspondence to Patricia Diaz-Gimeno.

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Marti-Garcia, D., Sebastian-Leon, P., Dolz del Castellar, P. et al. Endometrial cortisol level and its relationship with psychological stress, molecular tissue changes, and clinical outcomes in infertile women. Sci Rep (2026). https://doi.org/10.1038/s41598-026-41233-8

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  • Received: 10 November 2025

  • Accepted: 18 February 2026

  • Published: 24 February 2026

  • DOI: https://doi.org/10.1038/s41598-026-41233-8

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Keywords

  • State-Trait Anxiety Inventory (STAI)
  • Cortisol
  • Stress biomarkers
  • Endometrial microenvironment
  • Endometrial factor in infertility
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