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Multicenter Study
. 2025 Aug:168:28-34.
doi: 10.1016/j.placenta.2025.05.026. Epub 2025 May 29.

Hystero-embryoscopy as a tool for RPL immunological research at the maternal-fetal interface

Valentina Bruno  1 , Brunella Zizolfi  2 , Margherita Ferretti  3 , Simona Di Martino  4 , Ana Maria Arteni Brindusa  4 , Martina Betti  5 , Ludovica Ciuffreda  3 , Francesca De Nicola  3 , Stefano Scalera  5 , Federica Cariati  2 , Chiara De Angelis  6 , Fabiola Nardelli  2 , Matteo Giudice  2 , Emanuela Mancini  7 , Ermelinda Baiocco  7 , Mario Russo  2 , Matteo Pallocca  8 , Maurizio Fanciulli  3 , Giulia Piaggio  3 , Mariantonia Carosi  9 , Attilio Di Spiezio Sardo  2 , Enrico Vizza  7
Affiliations
Multicenter Study

Hystero-embryoscopy as a tool for RPL immunological research at the maternal-fetal interface

Valentina Bruno et al. Placenta. 2025 Aug.

Abstract

Introduction: An abnormal immune response at the fetal-maternal interface is expected in 50-60 % of unexplained Recurrent Pregnancy Loss (uRPL) cases. Detected immunophenotypes in uRPL could help in risk assessment, prognosis and therapy. The study of immune mechanisms at the fetal-maternal interface is crucial, but the technique used for research has limitations, including contamination and invasiveness, which can trigger immune responses. Hystero-embryoscopy may provide a precise method for studying the immunological factors involved in RPL at the maternal-fetal interface, reducing bias from sample collection techniques. Our aim is to assess its effectiveness in obtaining high-quality samples to study the immunological basis of RPL.

Methods: This is a multicenter prospective study in which 10 women with a first-trimester ongoing miscarriage were enrolled and received surgical treatment at the University Hospital Federico II in Naples. Embryo-hysteroscopy was used to selectively obtain decidual and chorionic villous tissues separately, from the maternal-fetal interface. Transcriptome sequencing was performed at Regina Elena National Cancer Institute in Rome.

Results: RNA integrity numbers (RIN) satisfied the minimum quality requirements (median RIN considering all samples was 8.4 ± 1.1) and RNA sequencing exhibited adequate sequencing depth (the mean of Uniquely Mapped Reads considering all samples was 52.1 ± 7.7), ensuring reliable downstream analysis. The bioinformatics analysis demonstrated the absence of cross-tissue contamination due to the clear separation between the transcriptional profiles of decidual and chorionic villous tissues: CD45 immunostaining and pathological validation confirmed these findings.

Conclusions: These findings demonstrate that hystero-embryoscopy enables precise immunological profiling at the maternal-fetal interface while minimizing sample contamination.

Keywords: Decidua; Immune microenvironment; Inflammation; Recurrent pregnancy loss; Trophoblast.

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Conflict of interest statement

Declaration of competing interest All the authors declare that they have no conflict of interest.

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