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Published on: August 4, 2021
Maternal-fetal interface abnormalities in unexplained recurrent pregnancy loss: mechanisms, models, and a framework
Asahi Tokuoka1, Kiriko Iida2, Mitsutoshi Yamada1
1Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
Frontiers in Endocrinology
|August 14, 2026
Summary
Unexplained recurrent pregnancy loss (URPL) may stem from maternal-fetal interface issues. New technologies allow detailed study of these cellular and molecular defects, potentially leading to new URPL classifications.
Area of Science:
- Reproductive Biology
- Immunology
- Genetics
Background:
- Recurrent pregnancy loss (RPL) is a complex condition, with unexplained recurrent pregnancy loss (URPL) lacking a defined cause after standard evaluation.
- URPL is currently an exclusion-based category, encompassing recurrent miscarriage (RM) and recurrent spontaneous abortion (RSA), distinct from recurrent implantation failure (RIF).
Purpose of the Study:
- To review the hypothesis that URPL arises from cellular and molecular abnormalities at the maternal-fetal interface.
- To explore recent advances in molecular and cellular technologies for investigating these interface defects.
Main Methods:
- Focus on maternal (endometrial, decidual, immune) and fetal/trophoblast compartments.
- Incorporation of insights from single-cell, spatial, organoid, assembloid, and placental explant studies (2024-2026).
Main Results:
- Current data do not support established clinical subtypes or routine treatment selection for URPL.
- Emerging technologies enable high-resolution phenotyping of the maternal-fetal interface.
Conclusions:
- An interface-centered framework is crucial for advancing URPL research.
- This approach may enable the identification of experimentally testable subtypes based on specific cellular and molecular phenotypes.
