UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

X-chromosome inactivation and FMR1 CGG repeat and AGG interspersion number in female newborns conceived by assisted reproductive technologies (ARTs) Wu, Elizabeth Xianshi


Pregnancies derived from in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are associated with increased rates of chromosome abnormalities, congenital malformations, low birth weight, pre-term births, multiple gestations, and imprinting disorders. Assisted reproductive technologies (ARTs) enable sub-fertile individuals to circumvent the natural selective pressures involved in human reproduction. The risks of ARTs may be due to the underlying causes of subfertility in these individuals or to the artificial processes used to achieve pregnancy. X-chromosome inactivation (XCI) may be at risk to perturbations in ARTs as it is thought to occur during the blastocyst stage when in vitro culturing would be taking place. We examined the XCI status in females conceived by ICSI (n=70), IVF (n=68), and naturally (NC, n=42). We found no significant differences between the populations in the frequency of mild skewing (≥75%) or extreme skewing (≥90%), or the mean level of skewing. Two extremely skewed cases were identified (1 IVF and 1 NC). It was determined that the maternal allele was preferentially inactivated in the cord blood of the extremely skewed IVF case. XCI status between placental sites varied in this case, but skewing values tended to correlate between different tissues within the same site. Furthermore, it is possible that infertile individuals are passing on high repeat FMR1 alleles associated with infertility or that repeat expansion could be occurring in subfertile parent’s germlines or during in vitro culturing. We investigated FMR1 CGG repeat and AGG interspersion number in the alleles of females conceived by ICSI (n=36), IVF (n=36), and NC (n=36). We did not find a significant difference between the populations in the frequency of intermediate alleles (45-54 repeats), premutation alleles (55-200 repeats), the mean allele repeat number, the biallelic mean, the distribution of FMR1 genotypes, or the distribution of total AGG interspersion number. No full mutation alleles were observed. A single premutation allele was found in a NC infant. The results indicate that female newborns conceived through ICSI and IVF are not at a greater risk of having skewed XCI or of inheriting FMR1 alleles with higher CGG repeat counts and more instability than female newborns conceived naturally.

Item Media

Item Citations and Data


Attribution-NonCommercial-NoDerivatives 4.0 International