Male and female meiotic behaviour of an intrachromosomal insertion determined by preimplantation genetic diagnosis

Abstract

BackgroundTwo related family members, a female and a male balanced carrier of an intrachromosomal insertion on chromosome 7 were referred to our centre for preimplantation genetic diagnosis. This presented a rare opportunity to investigate the behaviour of the insertion chromosome during meiosis in two related carriers. The aim of this study was to carry out a detailed genetic analysis of the preimplantation embryos that were generated from the three treatment cycles for the male and two for the female carrier.Patients underwent in vitro fertilization and on day 3, 22 embryos from the female carrier and 19 embryos from the male carrier were biopsied and cells analysed by fluorescent in situ hybridization. Follow up analysis of 29 untransferred embryos was also performed for confirmation of the diagnosis and to obtain information on meiotic and mitotic outcome.ResultsIn this study, the female carrier produced more than twice as many chromosomally balanced embryos as the male (76.5% vs. 36%), and two pregnancies were achieved for her. Follow up analysis showed that the male carrier had produced more highly abnormal embryos than the female (25% and 15% respectively) and no pregnancies occurred for the male carrier and his partner.ConclusionThis study compares how an intrachromosomal insertion has behaved in the meiotic and preimplantation stages of development in sibling male and female carriers. It confirms that PGD is an appropriate treatment in such cases. Reasons for the differing outcome for the two carriers are discussed.

Meiotic Behaviour of Chromosomes Involved in Structural Chromosomal Abnormalities Determined by Preimplantation Genetic Diagnosis

“…Munne et al (2000) reported that the meiotic segregation patterns found at female carriers of Robertsonian translocations were different from those described in male carriers, with females showing a higher level of unbalanced gametes, however this observation was not confirmed by later studies (Munne, 2005). However for one family with an intrachromosomal insertion there seemed to be an effect of the sex of the carrier parent on the mode of segregation (Xanthopoulou et al, 2010).…”

“…A high level of mosaicism has been reported in embryos from reciprocal translocation carriers (Simopoulou et al, 2003), Robertsonian translocation carriers (Conn et al, 1998) as well as other forms of structural abnormalities such as intrachromosomal insertions (Xanthopoulou et al, 2010). As far as the embryos from translocation carriers are concerned, Iwarsson et al (2000) reported that the chromosomes involved in the translocation show an even higher degree of mosaicism when compared to control chromosomes.…”

“…Full follow up analysis on 22 untransferred embryos from a female carrier and 19 embryos from a male carrier of the same intrachromosomal insertion, indicated that the female carrier produced far more balanced embryos (45% versus 16%, Xanthopoulou et al, 2010).…”

“…However women of advanced maternal age referred for PGD for reciprocal translocations have reduced chances of achieving a pregnancy (Xanthopoulou et al, 2010) due to the high level of meiotic aneuploidy for chromosomes other than the ones involved in the aberration as well as due to malsegregation of the aberration chromosomes.…”

PGD for a carrier of an intrachromosomal insertion using aCGH

“…Only two studies on the use of PGD for carriers of an intrachromosomal insertion have been previously reported, both using interphase fluorescence in-situ hybridization (FISH) technology performed on blastomeres following day 3 embryo biopsy [Simopoulou et al 2003;Xanthopoulou et al 2010]. We present the first published case of PGD using array comparative genomic hybridization (aCGH) following trophectoderm biopsy for a carrier of an intrachromosomal insertion.…”