Peri-implantation hormonal milieu: Elucidating mechanisms of abnormal placentation and fetal growth

Monica A. Mainigi, Devvora Olalere, Irina Burd, Carmen Sapienza, Marisa Bartolomei, Christos Coutifaris

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Assisted reproductive technologies (ART) have been associated with several adverse perinatal outcomes involving placentation and fetal growth. It is critical to examine each intervention individually in order to assess its relationship to the described adverse perinatal outcomes. One intervention ubiquitously used in ART is superovulation with gonadotropins. Superovulation results in significant changes in the hormonal milieu, which persist during the peri-implantation and early placentation periods. Epidemiologic evidence suggests that the treatmentinduced peri-implantation maternal environment plays a critical role in perinatal outcomes. In this study, using the mouse model, we have isolated the exposure to the peri-implantation period, and we examine the effect of superovulation on placentation and fetal growth. We report that the nonphysiologic peri-implantation maternal hormonal environment resulting from gonadotropin stimulation appears to have a direct effect on fetal growth, trophoblast differentiation, and gene expression. This appears to be mediated, at least in part, through trophoblast expansion and invasion. Although the specific molecular and cellular mechanism( s) leading to these observations remain to be elucidated, identifying this modifiable risk factor will not only allow us to improve perinatal outcomes with ART, but help us understand the pathophysiology contributing to these outcomes.

Original languageEnglish (US)
Article numberArticle 26
JournalBiology of reproduction
Issue number2
StatePublished - Feb 2014
Externally publishedYes


  • ART
  • Epigenetics
  • Estradiol
  • Gonadotropins
  • Implantation

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology


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