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Investigation of confined placental mosaicism and aberrant H19/ IGF2 imprinting in pregnancies conceived by in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI)

University of British Columbia

In-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are two of the most common forms of assisted reproductive technologies (ARTs) used to treat human infertility. Presently, over two million children have been conceived by ART. The majority of these children are born healthy. However, IVF and ICSI have been associated with increased risks of adverse perinatal health outcomes. The higher risk of low birth weight, intrauterine growth restriction, and small for gestational age are of special concern due to its association with adult-onset diseases. In this thesis project, the effect of ART on the genetic and epigenetic status of the placenta, and their associations with fetal growth restriction are examined. In the first objective, placentas from IVF and ICSI pregnancies were investigated for the presence of confined placental mosaicism (CPM). Of all cases, CPM was not detected in IVF and ICSI placentas that were appropriate for gestational age (AGA). CPM was not detected in any of the IVF or ICSI cases that were small for gestational age (SGA). By pooling the results from this study, and previous results from this lab, it was determined that the prevalence of CPM in ART pregnancies (3.7%) was higher, but not significant, when compared to the reported literature on natural conceptions (2.22%; p=0.23). In the second objective of this study, DNA methylation at the imprinting control region 1 (ICR1) of the genes H19 and IGF2, was investigated in the placentas from IVF, ICSI and natural conceptions. SGA pregnancies were also compared to AGA pregnancies. A multiple comparison analysis did not reveal any significant differences in mean DNA methylation levels in IVF, ICSI, or natural conceptions that were AGA or SGA (p=0.49). Although hypomethylation was detected in all groups, they did not appear to bear a significant clinical effect. Hypomethylation was defined as a value of less than 2 standard deviations from the mean methylation value at each CpG site analyzed. These results demonstrate that placental abnormalities may not be more prevalent in ART conceptions than natural conceptions. Further study of other plausible biological mechanisms in causing adverse perinatal health outcomes in ART is recommended.

Text

2011-04-20

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/33832

Reproductive and Developmental Sciences

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/