*Review* **Endometrial Decidualization: The Primary Driver of Pregnancy Health**

**Shu-Wing Ng 1,2,\*, Gabriella A. Norwitz <sup>3</sup> , Mihaela Pavlicev <sup>4</sup> , Tamara Tilburgs 5,6 , Carlos Simón 7,8,9 and Errol R. Norwitz 1,2,\***


Received: 24 April 2020; Accepted: 5 June 2020; Published: 8 June 2020

**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.

**Keywords:** endometrium; decidualization; adverse pregnancy outcome; preconception
