Multiple aneuploidies in the oocytes of balanced translocation carriers: a preimplantation genetic diagnosis study using first polar body

Abstract

Preimplantation genetic diagnosis (PGD) of first polar bodies (1PBs) has been used in carriers of balanced chromosomal reorganizations and also for aneuploidy screening. Although an acceptable number of normal or balanced embryos is usually obtained using PGD in translocation carriers, the pregnancy rate is disappointingly low. To determine whether aneuploidy of chromosomes not involved in the chromosome rearrangements could be the cause of the low pregnancy rates achieved, the present authors analysed the segregation products of three translocation carriers, t(8;13)(q24.1;q22) and two Robertsonian (Rob)(13;14), using 1PBs, and afterwards another eight chromosomes in the same 1PBs, for a total of 10 chromosomes in each 1PB, that is chromosomes 1, 8, 13, 14, 15, 16, 17, 18, 21, 22 and X. In the reciprocal translocation, chromosomes with different chromatids due to meiotic recombination were found. Only one out of nine 1PBs was normal for the reorganization products but no aneuploidies were found after PGD in this case. In the two balanced Rob(13;14), six out of 12 and four out of 11 1PBs were normal or balanced for the reorganization but only one oocyte was euploid for all the chromosomes analysed in each case; a single embryo transfer was made in both but no pregnancy was achieved. The incidence of aneuploidy for the chromosomes not involved in the Robertsonian translocations was extremely high (91.7% and 81.8%). Extra chromosomes were present in most of the aneuploid oocytes (81.8% and 90%). The reason for this increase could be the tendency to non-disjunction related to advanced maternal age combined with an interchromosomal effect resulting in the presence of synaptic errors in other chromosome pairs.

Chromosomal analysis of blastocysts from balanced chromosomal rearrangement carriers

“…Therefore, PGD based on cleavage-stage FISH for CR carriers may not accurately detect the imbalance of CR-associated chromosomes and effectively reflect the chromosomal composition in the corresponding blastocysts. Moreover, aneuploidy is common in embryos from CR carriers (Pujol et al 2003), even those that are normal/balanced for CR-associated chromosomes (Pujol et al 2006, Treff et al 2011, and CR-associated chromosomes can exert inter-chromosomal effects during meiosis and mitosis (Lejeune 1963, Pellestor et al 1989, Conn et al 1998, Munne et al 2005a, leading to an increased risk of chromosomal abnormality. As such, aneuploidy screening is recommended in parallel with the detection of CR-associated imbalances.…”

Preconceptional diagnosis for Robertsonian translocation as an alternative to preimplantation genetic diagnosis in two situations: a pilot study

“…A few studies of PGD in translocation carriers using blastomeres have been published, reporting a high aneuploidy rate in patients with previous miscarriage or termination of pregnancy (for example, 72% abnormality rate for Robertsonian translocation and 82% for reciprocal translocation [10,11]). Equivalent high aneuploidy rates (for example, 69.0% [12] and 65.5%, [13], respectively) are also obtained by PB1 analysis. For women with no particular obstetric history, included because of male infertility, few cases have been reported and no conclusion has been reached [14].…”

Causative Mutations and Mechanism of Androgenetic Hydatidiform Moles

“…In humans, the MSUC can also be triggered by abnormal homologous chromosome synapsis in carriers of reciprocal translocations, which are well documented to be associated with infertility and recurrent miscarriages in male and female carriers. [44][45][46] With respect to HMs, two of the original reports about androgenetic monospermic CHMs found that 4%-6% of affected women had balanced chromosomal translocations, which is higher than the frequency of reciprocal translocation in the general population (0.6%). 3,47 Miscarriages are a well-known risk factor for sporadic HMs 48 and sporadic HMs are more frequent in women with recurrent miscarriages than in women from the general population.…”