Placental Dysfunction in Assisted Reproductive Pregnancies: Perinatal, Neonatal and Adult Life Outcomes

Abstract

Obstetric and newborn outcomes of assisted reproductive technology (ART) pregnancies are associated with significative prevalence of maternal and neonatal adverse health conditions, such as cardiovascular and metabolic diseases. These data are interpreted as anomalies in placentation involving a dysregulation of several molecular factors and pathways. It is not clear which extent of the observed placental alterations are the result of ART and which originate from infertility itself. These two aspects probably act synergically for the final obstetric risk. Data show that mechanisms of inappropriate trophoblast invasion and consequent altered vascular remodeling sustain several clinical conditions, leading to obstetric and perinatal risks often found in ART pregnancies, such as preeclampsia, fetal growth restriction and placenta previa or accreta. The roles of factors such as VEGF, GATA3, PIGF, sFLT-1, sEndoglin, EGFL7, melatonin and of ART conditions, such as short or long embryo cultures, trophectoderm biopsy, embryo cryopreservation, and supraphysiologic endometrium preparation, are discussed. Inflammatory local conditions and epigenetic influence on embryos of ART procedures are important research topics since they may have important consequences on obstetric risk. Prevention and treatment of these conditions represent new frontiers for clinicians and biologists involved in ART, and synergic actions with researchers at molecular levels are advocated.

Programmed frozen embryo transfer cycles are associated with a higher risk of abnormal placental development: a retrospective cohort study of singleton live births

“…Placenta not only regulates the development of the fetus, but also dysplasia of placenta will lead to poor maternal and perinatal outcomes as well as long-term health risks later in life, including neurodevelopmental disorders, tumors, and adult metabolic syndrome ( 10 , 11 ). There is sufficient evidence that ART may be related to changes in placental morphology and structure, growth dynamics, imprinted and non imprinted genes, and other aspects that regulate placental formation ( 12 , 13 ). Several studies have shown that the incidence of placenta previa in ART is significantly higher than in natural pregnancy ( 14 ).…”

Peculiarities of the morphology of the placenta of women with premature birth

“…Для виконання плацентою своїх функцій принциповою умовою є достатня її маса. Крім відносності достатності маси (її надлишкового резерву), слід враховувати, що йдеться насамперед про масу функціонуючих клітин, адже органна маса (як і об'єм) є величиною інтегральною (а значить орієнтовною), яка включає в плаценті також екстрацелюлярний матрикс, фібриноїд, плодову кров та залишки материнської крові, кальцифікати, можливі некротичні ділянки, кісти тощо [17][18][19][20]. Значущість цих структурних компонентів у функціональному аспекті нерівнозначна.…”

Polygenic risk score for embryo selection—not ready for prime time

“…However, if IVF and PRS-ES are undertaken solely for the purposes of PRS-ES, the future person could, in one sense, be harmed by PRS if that procedure exposes him or her to avoidable risks. For example, PGT has been associated with certain uncommon side effects in pregnancy ( Makhijani et al , 2021 ), which may have long-term consequences ( Manna et al , 2022 ). Multiple medical conditions also appear to be more prevalent in ART-conceived individuals compared to their naturally conceived peers ( Chen and Heilbronn, 2017 ; von Wolff and Haaf, 2020 ; Luke, 2021 ).…”