An overview of periconceptional pathology and pathophysiology: Where do we go next?

James M Roberts; Graham J Burton; Kirk P Conrad; Barbara Luke; Mellissa Rw Mann; Ashley Moffett; McKenzie K Jancsura

doi:10.1016/j.placenta.2025.06.010

An overview of periconceptional pathology and pathophysiology: Where do we go next?

Placenta. 2025 Jun 11:168:98-110. doi: 10.1016/j.placenta.2025.06.010. Online ahead of print.

Authors

James M Roberts¹, Graham J Burton², Kirk P Conrad³, Barbara Luke⁴, Mellissa Rw Mann⁵, Ashley Moffett⁶, McKenzie K Jancsura⁷

Affiliations

¹ Department of Obstetrics, Gynaecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Magee-Womens Research Institute, Pittsburgh, PA, USA; Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA; Clinical and Translational Research, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: jroberts@mwri.magee.edu.
² Department of Physiology, Development and Neuroscience and Loke Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
³ Departments of Physiology, and of Obstetrics and Gynecology University of Florida College of Medicine, Gainesville, FL, USA.
⁴ Department Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, East Lansing, MI, USA.
⁵ Department of Obstetrics, Gynaecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Magee-Womens Research Institute, Pittsburgh, PA, USA.
⁶ Department of Pathology, and Loke Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
⁷ Martha S Pitzer Center for Women, Children and Youth, College of Nursing, The Ohio State University, Columbus, OH, USA.

PMID: 40517487
DOI: 10.1016/j.placenta.2025.06.010

Abstract

It is becoming increasingly evident that studies of pregnancy and pregnancy complications must begin earlier in pregnancy than has typically been the case. Important events with effects through and beyond pregnancy take place in the periconceptional period, from shortly before to shortly after conception. During this time ovarian hormones act not only to facilitate successful implantation but also direct maternal physiological adaptations necessary for pregnancy. Decidua also undergoes changes necessary for successful implantation of the embryo. These involve not only maternal preparation of a receptive site for implantation but interactions, including immunological and others, of cells of the maternal decidua and embryo. All of this occurs in a setting in which the cells of the embryo are involved in complex epigenetic changes. Assisted reproductive technology (ART) has the potential to influence many of these since ART typically occurs at this time of these epigenetic change. Many of the variables involved in ART have the potential to influence epigenetic adaptation. In fall of 2023 the Global Pregnancy Collaboration brought together experts in these areas to consider the status of our understanding of the periconceptional period. This manuscript presents an update of this information including new approaches to study these very early events. The potential impact of ART on periconceptional events and the mechanisms involved are presented. Based upon this information recommendations are made for future research in these important areas.

Keywords: Assisted reproductive technology; Corpus luteum; Decidua; Imprinting; Periconceptional; Uterine natural killer cells.

Publication types

Review