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Immune altering role of progesterone in pregnancy

Immune altering role of progesterone in pregnancy

New insights are emerging into the immune altering role of progesterone and subsequent development of preeclampsia in artificial cycles of frozen embryo transfer (FET).

A letter1 by Dr Rasha Al-Lami MDfrom the department of Obstetrics, Gynecology and Reproductive Sciences, at McGovern Medical School from The University of Texas Health Science Center, responds to a Science Direct journal article by Conrad, von Versen-Höynck, and Bakertitled ‘Risk of preeclampsia in artificial frozen embryo transfer as a result of insufficient corpus luteum hormone levels.’ 2

Dr Al-Lami has previously researched the possible immune altering roles of less than physiological levels of estrogen in the development of preeclampsia and placenta accrete spectrum in women conceived by artificial cycles (AC) of FET.3,4  Recent research shows suboptimal levels of progesterone may also contribute to abnormal decidualisation and potentially to preeclampsia development in FET-AC through immune response alteration.

Dr Al-Lami explains:

“Normally in pregnant women, endogenous progesterone can modulate the function of the innate and cellular immune response systematically and locally in maternal-fetal interface, and exhibit a net anti-inflammatory effects for successful pregnancy. It was found that progesterone can inhibit the activation of various inflammatory cells (including uterine macrophages), suppress the NF-kB signaling pathway, increase anti-inflammatory cytokines (e.g., IL-10), and decrease proinflammatory ones (e.g., TNF-a).”

Dr Al-Lami draws the following conclusions:

“Progesterone favors Th-2 response over Th-1 with subsequent heightened humoral relative to T-lymphocyte cellular immune response that subsequently mitigates the inflammatory reaction. It is thus reasonable that suboptimal levels of progesterone (as found in FET-AC) may lead to improper decidualization, placental ischemia and preeclampsia development in addition to tolerance failure to paternal antigens and augmented inflammatory response that collectively results in higher risk of HDP and preeclampsia.

It is therefore interesting to know and would be appreciated if Conard and colleagues can discuss other potential pathways through which suboptimal hormonal levels contribute to the development of HDP and preeclampsia in women conceived by FET-AC in addition to hormones’ immune altering roles that affect decidualization and subsequent placentation, and their synergistic effects with relaxin.”

This closed access letter from Dr Al-Lami is available to read here.


  1. AL-LAMI RA, Immune Altering Roles of Progesterone and Subsequent Development of Preeclampsia in Artificial Cycles of Frozen Embryo Transfer, American Journal of Obstetrics and Gynecology (2022), doi:
  • Al-Lami RA, Sibai BM, Salih SM. Risk of Preeclampsia in Artificial Cycles of Frozen Embryo Transfer In Vitro Fertilization Pregnancies. American Journal of Obstetrics & Gynecology. doi:10.1016/j.ajog.2021.06.065
  • Al-Lami RA, Salih SM, Sibai BM. In vitro fertilization as an independent risk factor for placenta accreta spectrum. Am J Obstet Gynecol. Dec 2021;225(6):699. doi:10.1016/j.ajog.2021.08.008
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