Medically assisted reproduction significantly affects the expression of microRNA associated with adverse obstetric outcomes.

RESEARCH QUESTION: Do normal term pregnancies conceived by medically assisted reproduction (MAR) differ in the expression of microRNA associated with adverse obstetric outcomes compared with normal term pregnancies after natural conception, and are there differences in microRNA expression profiles between MAR groups?

DESIGN

This retrospective case-control study examined 103 pregnancies conceived by MAR and 79 pregnancies conceived naturally. The expression of 29 microRNA associated with adverse obstetric outcomes was evaluated in maternal peripheral blood leukocytes collected at 10-13 weeks of gestation.

RESULTS

Pregnancies after MAR showed significant changes in expression of 4-9 microRNA depending on the specific MAR group (IVF/intracytoplasmic sperm injection [ICSI] fresh embryo transfer group, 9 microRNA; intrauterine insemination group, 6 microRNA; IVF/ICSI frozen embryo transfer group, 4 microRNA) compared with pregnancies after natural conception in the early stages of pregnancy. Remarkably, some of these changes overlapped with those found in the early stages of pregnancies with a subsequent occurrence of pre-eclampsia, HELLP syndrome, fetal growth restriction, small for gestational age, gestational diabetes, preterm delivery without other pregnancy complications, miscarriage or stillbirth.

CONCLUSIONS

This study is the first to show that even normal term pregnancies after MAR show significantly altered microRNA expression profiles in the first trimester of gestation compared with pregnancies after natural conception. The degree of dysregulation in microRNA expression varied depending on the MAR used, and the observed changes were partially consistent with those found in pregnancies that later developed pregnancy-related complications. These findings suggest that MAR significantly affects the epigenetic profile.