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.
Highlights
There is a rapidly increasing interest in placentation in obstetric adverse outcome, neonatal and adult life health after infertility, and its related therapies
We provide a summary of the most recent literature on placental dysfunction associated with obstetric, perinatal outcomes in singletons born after NONART and assisted reproductive technology (ART) treatments
An altered expression of factors and molecules involved in proper placental developremodeling and placenta hypoperfusion, sustain several clinical conditions leading to ment, leading to impaired trophoblast invasion and subsequent reduced vascular remodelobstetric and perinatal risks often found in ART pregnancies, such as PE, fetal growth restriction (FGR) and ing and placenta hypoperfusion, sustain several clinical conditions leading to obstetric and placenta previa or accrete (Figure 1) [24,25,26,27,28]
Summary
There is a rapidly increasing interest in placentation in obstetric adverse outcome, neonatal and adult life health after infertility, and its related therapies. Abnormal placentation and obstetric complications such as PTB, preeclampsia (PE), and fetal growth restriction (FGR) have been associated with endometriosis, a common factor of infertility [2] Another maternal condition at risk for the development of placental anomalies, commonly associated with infertility, is polycystic ovary syndrome (PCOS), in which the prevalence of gestational diabetes mellitus (GDM) is significantly increased [3]. ART is associated with increased risk of epigenetic alterations influencing gene expression and DNA methylation in early development and in the placenta, eventually triggering diseases and affecting long-term health [20,21,22] These findings support the hypothesis of a primary ART responsibility for adverse perinatal outcomes with evident suspicions for anomalies of placentation, fertility treatments themselves are often associated with impaired placentation and related adverse pregnancy outcomes [1]. This review is based on systematic reviews (SRs), large cohort studies, meta-analyses, and genetic, epigenetic and molecular studies
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