Endometrial Transcriptome Changes following Short-Term Liraglutide Treatment in Infertile Women with Polycystic Ovarian Syndrome and Obesity

Vesna Salamun; Luca Lovrecic; Ales Maver; Borut Peterlin; Helena Ban Frangez; Gaetano Riemma; Antonio Simone Laganà; Rok Herman; Andrej Janez; Eda Vrtacnik Bokal; Mojca Jensterle

doi:10.1159/000547513

Endometrial Transcriptome Changes following Short-Term Liraglutide Treatment in Infertile Women with Polycystic Ovarian Syndrome and Obesity

Gynecol Obstet Invest. 2025 Jul 22:1-10. doi: 10.1159/000547513. Online ahead of print.

Authors

Vesna Salamun^{1

2}, Luca Lovrecic^{2

3}, Ales Maver^{2

3}, Borut Peterlin^{2

3}, Helena Ban Frangez^{1

2}, Gaetano Riemma⁴, Antonio Simone Laganà⁵, Rok Herman^{2

6}, Andrej Janez^{2

6}, Eda Vrtacnik Bokal^{1

2}, Mojca Jensterle^{2

6}

Affiliations

¹ Division of Obstetrics and Gynecology, Department of Human Reproduction, University Medical Centre Ljubljana, Ljubljana, Slovenia.
² Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
³ Clinical Institute of Medical Genetics, University Medical Centre Ljubljana, Ljubljana, Slovenia.
⁴ Obstetrics and Gynecology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.
⁵ Unit of Obstetrics and Gynecology, "Paolo Giaccone" Hospital, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy.
⁶ Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia.

PMID: 40695252
DOI: 10.1159/000547513

Abstract

Objectives: The aim of the study was to evaluate whether the use of a 12-week liraglutide treatment changes the endometrial gene expression during the implantation window in infertile obese women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilization (IVF).

Design: A cross-sectional study involving treated and non-treated subjects was conducted.

Participants: Infertile women with PCOS and BMI ≥30 kg/m2 participated in the study.

Setting: The study was conducted at a tertiary-care university hospital.

Methods: Endometrial biopsies were collected from 20 infertile women during the implantation window, 1 month prior to entering the IVF procedure. Endometrium transcriptome of 10 participants, who had been pretreated with low-dose liraglutide 1.2 mg QD for 12 weeks and achieved at least a 5% reduction in body weight, was compared to endometrium transcriptome of 10 treatment-naive participants, who had a stable body weight over the last 12 weeks. Next-generation sequencing was conducted to analyze RNA from the samples. The resulting data were processed to discern key canonical pathways and predict activations or inhibitions. Gene networks were constructed based on established published associations.

Results: Gene Set Analysis (GSA) identified a total of 17 canonical pathways that were significantly differentially expressed between the two groups. The most important canonical pathways included GLP-1 receptor activation, modulation of inflammation and oxidative stress response, alterations in glucose homeostasis, and energy consumption, with YWHAG being a notable central gene in the associated network. The results indicate a possible involvement of the AKT pathway in the liraglutide mode of action.

Limitations: The main limitations include its cross-sectional design and considerable number of upregulated and downregulated genes.

Conclusions: Short-term low-dose liraglutide treatment prior to IVF was associated with changes in the endometrial transcriptome that could potentially be important for improving endometrial receptivity and fertility in women with obesity and PCOS.

Keywords: Endometrial gene expression; In vitro fertilization; Liraglutide treatment; Obesity; Polycystic ovarian syndrome; Transcriptomic analysis.