Endometrial Decidualization: The Primary Driver of Pregnancy Health

Shu-Wing Ng; Gabriella A Norwitz; Mihaela Pavlicev; Tamara Tilburgs; Carlos Simón; Errol R Norwitz

doi:10.3390/ijms21114092

Pregnancy · Preconception Care

Endometrial Decidualization: The Primary Driver of Pregnancy Health

Ng SW, Norwitz GA, Pavlicev M, Tilburgs T, Simón C, Norwitz ER

Published June 8, 2020 International Journal of Molecular Sciences, 21(11), E4092

DOI 10.3390/ijms21114092 PMID 32521725 PMC PMC7312091

RRM Academy Synopsis

The uterine lining may set pregnancy health before conception

A 2020 review of published studies argues that pregnancy health may be set by the uterine lining before an embryo arrives. In humans, the lining starts preparing in the second half of each cycle, a step called decidualization. Poor readiness could weaken implantation and cause problems later. The paper offers an idea and reports no new patient data.

Key Findings

In humans, the lining begins decidualization in the second half of every menstrual cycle, whether or not an embryo is present. Few mammal species work this way.
The best-case chance of pregnancy in one cycle peaks at 30%. Only 50% of conceptions go past 20 weeks, and 75% of pregnancies that fail do so because implantation fails.
The lining is most receptive during a personalized window of 24–36 h. Implantation outside that window fails or raises the risk of adverse pregnancy events.
One cited study found a decidualization defect in women with a history of severe preeclampsia, detected at delivery and persisting for years thereafter.
Cited studies suggest that women with recurrent pregnancy loss have impaired cyclic decidualization.

Interpretation

The authors gather published studies to support a hypothesis, and they report no new patient data. Several molecular studies they cite used cell cultures and mouse models. The cited human studies of preeclampsia and recurrent pregnancy loss involved women with those conditions or a history of them. The authors say the role of decidualization in human pregnancy is incompletely understood. Treatments aimed at it remain to be tested.

RRM Context

The review names progesterone, made after ovulation, as the major driver of decidualization. Ovulation and the luteal phase sit at the center of its model. Restorative reproductive medicine looks at cycle function before pregnancy as a matter of principle. The authors list IVF conception among several risk factors for conditions such as preeclampsia and preterm birth. They ask whether too little seminal fluid exposure plays a part.

Our editorial summary of this paper, not the article's abstract.

Abstract

Interventions to prevent pregnancy complications have been largely unsuccessful. We suggest this is because the foundation for a healthy pregnancy is laid prior to the establishment of the pregnancy at the time of endometrial decidualization. Humans are one of only a few mammalian viviparous species in which decidualization begins during the latter half of each menstrual cycle and is therefore independent of the conceptus. Failure to adequately prepare (decidualize) the endometrium hormonally, biochemically, and immunologically in anticipation of the approaching blastocyst-including the downregulation of genes involved in the pro- inflammatory response and resisting tissue invasion along with the increased expression of genes that promote angiogenesis, foster immune tolerance, and facilitate tissue invasion-leads to abnormal implantation/placentation and ultimately to adverse pregnancy outcome. We hypothesize, therefore, that the primary driver of pregnancy health is the quality of the soil, not the seed.

Topics

Pregnancy › Preconception Care › Preconception Optimization · Genetics and Immunology › Reproductive Immunology › Implantation Immunology · Reproductive Endocrinology › Luteal Phase › Luteal Phase Deficiency

Shu-Wing Ng, Gabriella A Norwitz, Mihaela Pavlicev, Tamara Tilburgs, Carlos Simón, Errol R Norwitz

S Ng, G Norwitz, M Pavlicev, T Tilburgs, C Simón, E Norwitz

PMID 32521725 32521725 DOI 10.3390/ijms21114092 10.3390/ijms21114092 Ng et al. 2020, Ng 2020

Keywords

Biomarkers

Endometrial Decidualization: The Primary Driver of Pregnancy Health

The uterine lining may set pregnancy health before conception

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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Keywords