Immunomodulatory Role of Natural Progesterone in Pregnancy: A Review

Pregnancy complications such as miscarriage, preterm birth (PTB), and luteal phase defects (LPD) are significant reproductive health issues globally, with both physical and psychological implications. This review aims to examine the role of natural progesterone in pregnancy-related disorders, specifically threatened and recurrent miscarriage, PTB, and LPD. Additionally, it examines how natural progesterone's immune-modulating actions, including both direct and indirect involvement, contribute to maintaining pregnancy.

This narrative review was conducted using PubMed, Google Scholar, and reference screening to identify English-language studies examining the role of natural progesterone in miscarriage, PTB, and LPD. Emphasis was placed on progesterone's immunomodulatory actions, including cytokine regulation and the activity of the progesterone-induced blocking factor (PIBF), and their relevance to pregnancy maintenance.

Natural progesterone demonstrates clinical benefit in managing threatened miscarriage, recurrent pregnancy loss, preterm labor, and LPD. Evidence shows that it is well-tolerated with manageable side effects, reducing miscarriage rates, preventing PTB, and improving LPD outcomes through its effects on the maternal-fetal interface. This review also highlights progesterone's dual immunomodulatory action, direct cytokine regulation, and indirect influence via PIBF, which together contribute to improved pregnancy maintenance and outcomes.

Natural progesterone supports pregnancy by preventing miscarriages, preterm labor, and LPD through its direct and indirect immunomodulatory mechanisms. Clinically, it is well-tolerated with no serious or unexpected adverse events. However, gaps remain in fully understanding its effectiveness, emphasizing the need for further research.