The Periconceptional Environment and Cardiovascular Disease: Does In Vitro Embryo Culture and Transfer Influence Cardiovascular Development and Health?

Abstract

Assisted Reproductive Technologies (ARTs) have revolutionised reproductive medicine; however, reports assessing the effects of ARTs have raised concerns about the immediate and long-term health outcomes of the children conceived through ARTs. ARTs include manipulations during the periconceptional period, which coincides with an environmentally sensitive period of gamete/embryo development and as such may alter cardiovascular development and health of the offspring in postnatal life. In order to identify the association between ARTs and cardiovascular health outcomes, it is important to understand the events that occur during the periconceptional period and how they are affected by procedures involved in ARTs. This review will highlight the emerging evidence implicating adverse cardiovascular outcomes before and after birth in offspring conceived through ARTs in both human and animal studies. In addition, it will identify the potential underlying causes and molecular mechanisms responsible for the congenital and adult cardiovascular dysfunctions in offspring whom were conceived through ARTs.

The programming of cardiovascular disease

“…A review of current knowledge of in vitro fertilization and later cardiovascular disease was recently published. 41 The placenta and programming cardiovascular disease…”

In�vitro fertilization and embryo transfer alter human placental function through trophoblasts in early pregnancy

“…after adjusting for several confounding factors, the risk of numerous adverse outcomes during the perinatal period, including miscarriage, premature birth, low birth weight, intra-uterine growth retardation and gestational hypertension, are higher in in vitro fertilization and embryo transfer (iVF-eT) cohorts than for spontaneous pregnancies (1)(2)(3). over the last few years, the early stages of mammalian embryonic development have been shown to be very sensitive to the microenvironment, with long term effects on fetal, postnatal and adult health (4)(5)(6). The developmental origins of health and disease hypothesis, based on the evidence that prenatal exposure to modified environmental conditions affects postnatal growth, metabolism and disease susceptibility in adulthood, has been altered to include the preimplantation stages of development (7,8).…”

Alteration in the expression of the renin-angiotensin system in the myocardium of mice conceived by in vitro fertilization†

“…Multicenter epidemiological studies have shown that the incidence of cardiovascular malformations in ART babies is markedly increased compared with that of naturally conceived offspring [9][10][11]. Furthermore, follow-up surveys of ART-conceived offspring have shown an increased risk of dysfunction [12] and remodeling in the cardiovascular system [13], including higher arterial blood pressure, altered vascular intima-media thickness, and compromised myocardial regulatory function [14]. Investigations using mouse models have further illustrated that ART-conceived offspring have abnormal vascular endothelial function and changes in lipid metabolism [15,16].…”