Diagnosing and preventing inherited disease: The use of first polar bodies for preimplantation diagnosis of aneuploidy

Abstract

A large proportion of patients undergoing in-vitro fertilization (IVF) are aged > or = 35 years. It has been estimated that in this age group, 50% of embryos are chromosomally abnormal, with aneuploidy being the major contributing factor. Since the origin of most aneuploidies is maternal meiosis I non-disjunction, unfertilized oocytes could be safely screened for aneuploidy by analysing their first polar bodies. To determine the feasibility of first polar body aneuploidy analysis, polar bodies were analyzed by fluorescence in-situ hybridization (FISH) using probes simultaneously for chromosomes X, Y, 18, 13/21 or X, Y, 18 and 16. Within 6 h of retrieval, 88% showed a normal segregation involving a single chromosome of each kind, with double-dotted hybridization signals, corresponding to dyads (chromosomes in metaphase I composed of two chromatids). The rest showed non-disjunction of full dyads (6%), or an unbalanced pre-division of dyads (6%), which gives a segregation of one chromatid or one dyad and a chromatid with the first polar body. But only 34% of polar bodies analysed 24 h after retrieval or later showed a normal segregation, with most of the other polar bodies showing balanced pre-division, with two separated hybridization signals for all the chromosomes analysed. The rates of non-disjunction and unbalanced pre-division after > or = 24 h in culture were similar to the rates in fresh oocytes. When both types of aneuploidy were considered together, an increase of aneuploidy with maternal age was detected, which although slight, was significant (P = 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Dynamic blastomere behaviour reflects human embryo ploidy by the four-cell stage

“…S8b,c), we observed localization of DNA within fragments (indicated by white arrow in DAPI images and solid black arrow in differential interference contrast (DIC)/merged images). We also observed fragments negative for DAPI staining (shown by dashed black arrow) adjacent to DAPI-positive fragments, indicating that some but not all fragments contain nuclear DNA and eliminating the possibility that these fragments were polar bodies, which should have degenerated or initiated degeneration by this stage of development23 (Supplementary Fig. S8a).…”

Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence

“…Although PCOS patients are typically characterized by producing an increased number of oocytes, they are often of poor quality, leading to lower fertilization, cleavage and implantation rates, and a higher miscarriage rate (Sengoku et al ., 1997; Ludwig et al ., 1999; Mulders et al ., 2003; Heijnen et al ., 2006; Weghofer et al ., 2007; Sahu et al ., 2008; Boomsma et al ., 2008). This evidence raises the issue that poor oocyte and embryo quality may contribute to increased aneuploidy rates (Munné et al ., 1995; Gianaroli et al ., 2003, 2007). However, recent data suggest that women with PCOS yield higher numbers of oocytes and produce more euploid embryos in IVF, but still result in lower pregnancy and increased miscarriage rates, which are not genetically associated with an increased risk for embryonic aneuploidy (Weghofer et al ., 2007).…”

Arrested human embryos are more likely to have abnormal chromosomes than developing embryos from women of advanced maternal age

“…Currently, PGS is performed in samples biopsied from polar bodies [10-13], cleavage embryos [14,15] or blastocysts [16,17]. It has been found that blastocysts have less mosaicism than cleavage embryos, thus most laboratories prefer blastocyst biopsy, in which multiple cells from the trophectoderm (TE) are biopsied and used for screening [8,9].…”