Tatjana Motrenko Simic, Human Reproduction Center, Budva, Montenegro

After so many years practicing ART and several millions children born as a result of in vitro fertilization, it is well known fact that pregnancies conceived after ART is with some additional risks compared with spontaneously conceived pregnancies. Data from national registries, health reports and large studies point out higher risk for adverse perinatal outcome: higher incidence of multiple pregnancy (one third is from ART), spontaneous abortions, preterm delivery, IUGR, higher incidence of preeclampsia and other pregnancy related complications, like placental abruption, placenta previa, gestational diabetes mellitus, cesarean delivery and slight increase in birth defects. According USA Health report for 20000 children born from ART, comparing with naturally conceived children, have twice as likely to have health defects, 4, 5 times are susceptible to digestive tract disorder, 3, 7 times have higher risk of bowel disorders, 4 times more likely to have cleft lip, 31% more likely to die in period before and after birth, 26% more likely to be small for their age. Part of the problem could be related to maternal age and multiple gestation, but even singleton pregnancies demonstrate increased rate of perinatal complications. The doubt still stays for cause – what is contribution of underlying reproductive pathology related to infertility and what use of ART methods. Epigenetic control and imprinting processes could be disrupt during ovarian stimulation and gametes manipulation in ART. Oocyte imprinted genes and epigenetic changes show methylation defects in stimulated cycles compared with spontaneously ovulated. Dynamic state of genome in periconceptional and perinatal period made it extremely susceptible for adverse effects on epigenetic modification and increased chance for adult disease. Embryonic and fetal period are clearly vulnerable to environmental factors, and acquired changes can persist transgenerationally, despite the lack of continued exposure. The loss of methylation occurs between fertilization and blastocyste stage, to be established again in developing embryo producing epigenetic reprogramming. Routine procedures in ART like embryo culture systems (mediums, length of cultivation), embryo transfer or other manipulations can alter very active epigenetic reprogram of embryo and more important, some of the acquired changes can be maintained for the rest of the life. The are some increased concerns regarding specific disorders like developmental disabilities, retinoblastoma, childhood cancers, chronic conditions ( autism, schizophrenia, Alzheimer disease, asthma), imprinting disorders, learning and behavioral disorders and reproductive effects, especially possibilities that some problems could be transmitted to next generations. It animal models change is enzymes related to blood pressure regulation and metabolic processes is noticed. Most of studies comparing spontaneously conceived children with ART children do not find significant differences in medical, cognitive and motoric health but concerns related to metabolic profile, blood pressure, fertility and many other health issues still remains. Further long term studies are needed for better understanding of possible ART effects.