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Investigation of confined placental mosaicism (CPM) at multiple sites in post-delivery placeentas derived through intracytoplasmic sperm injection (ICSI) Minor, Agata

Abstract

Background: Many post-intracytoplasmic sperm injection (ICSI) births have been reported. However, concerns have been raised regarding a higher incidence of congenital abnormalities and of low birth weight. The incidence of chromosomal abnormalities in the extra-embryonic tissue lineage, such as the placenta, has not yet been examined. Confined placental mosaicism (CPM) is a chromosomal discrepancy between fetal and placental cells. We set out to investigate whether CPM is an underlying cause of negative pregnancy outcome, including intrauterine growth restriction (IUGR) and congenital abnormalities, and whether it is more prevalent in the post-ICSI population than in the general population. Methods: Fifty one post-delivery placentas were collected from patients who had undergone ICSI. These were divided into two groups depending on pregnancy outcome. Group A (n=41) consisted of placentas from pregnancies with a normal outcome, while group B (n=10) consisted of placentas from pregnancies complicated by IUGR or congenital abnormalities. Three sites of each placenta were sampled for chorionic villi. The villi were digested to obtain trophoblast and chorionic stroma, from which DNA was extracted. The DNA was analyzed by comparative genomic hybridization (CGH) for chromosomal imbalances. Flow cytometry was performed on chorionic stromal cells to determine ploidy. Abnormalities detected by CGH or by flow cytometry were confirmed by fluorescence in situ hybridization (FISH). The prevalence of CPM in the general population was obtained from published studies. Results: Fifty of the fifty one placentas analyzed by CGH had a balanced chromosomal constitution. An abnormality was detected in group B (-10%), in a placenta from a child affected by spina bifida. CGH analysis showed a gain of 7q31>qter and a loss of Xp21>pter in the trophoblast at two sites. Flow cytometry analysis showed tetraploidy in two placentas from group A (-5%). The abnormalities were confirmed by FISH analysis. CPM was not detected in pregnancies affected by IUGR. The incidence of CPM in the total post-ICSI population was -6% (3/51). Conclusion: The incidence of CPM did not differ significantly between the two study groups. We did not find a higher incidence of CPM in the ICSI population compared to the general population.

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