Role of Preimplantation Genetic Diagnosis (PGD) in Current Infertility Practice

Abstract

Chromosome imbalances are the leading cause of pregnancy loss in humans and play major roles in male and female infertility. Within the past two decades, the development and application of preimplantation genetic diagnosis (PGD) has played an important role in infertility practices worldwide. The purpose of this review is to discuss, how PGD may be applied in combating numerical chromosomal abnormalities and in Robertsonian and reciprocal chromosome translocations. We shall consider prevalence and risk of each aberration, interchromosomal effects and rationale behind use of PGD in each case. Numerical chromosome abnormalities (aneuploidy and polyploidy) in particular affect a very high proportion of preimplantation embryos (~ 50%). Given that a majority of preimplantation embryos are aneuploid, PGD can be used to screen embryos and transfer euploid embryos to improve pregnancy rates and reduce spontaneous abortions. The rationale of utilize PGD to transfer only euploid embryos would seem sound, but controversies exist surrounding application of PGD for aneuploidy detection. To this end, we will discuss the dichotomy between favorable descriptive reports and less favorable randomized clinical trial data. This review will discuss the trend towards differing sources of embryonic DNA (e.g. polar body vs blastomere vs blastocyst) as well as development of novel technologies for 24 chromosomes analysis.

Application of FISH method for preimplantation genetic diagnostics of reciprocal and Robertsonian translocations

“…After PGD, live birth rate per couple varied between 0 and 100% (median 31%). Thus, PGD improves the live birth rate in couples with recurrent miscarriage [4,7,18,22] but for those carrying a structural chromosome abnormality, its efficiency still seems to be insufficient [36]. However, for couples who are carriers of translocations with increased risk of chromosomally unbalanced offspring and increased risk of recurrent miscarriages, the PGD is still a chance www.fhc.viamedica.pl to exclude misdiagnosis and to choose the embryo that could be transferred preferentially [12].…”

“…It has been estimated that 1 in 625 individuals carries a balanced chromosomal translocation [3]. Even phenotypically normal carriers of balanced chromosomal translocations may experience reduced fertility, spontaneous abortions or birth defects [4]. In couples suffering from recurrent miscarriage, the incidence of the couple being a carrier of a structural chromosome abnormality is approximately 4-5%, mainly including reciprocal (RCP) and Robertsonian (RT) translocations [5].…”

“…It should be noted that levels of unbalanced gametes will be significantly higher than the empiric risk of having a chromosomally unbalanced live birth. This is due to the fact that many, if not most, of the segregate products, will be spontaneously aborted early in development (depending on the chromosomes and size of the segment involved) [4,8].…”

Chromosomal disorders and male infertility

“…44 Nevertheless, carriers of balanced chromosomal translocations, while normal phenotypically, may experience reduced fertility, spontaneous abortions or birth defects. 45 Normal meiotic segregation of these translocations in the gametes can lead to duplication or deletion of the chromosomal regions involved in the translocation. 45 Reduced fertility in translocation carriers may in part be the result of the requirement during meiosis for chromosomal translocations to form a quadrivalent or trivalent structure (reciprocal and Robertsonian translocations, respectively) to enable homologous chromosomes to pair.…”

“…45 Normal meiotic segregation of these translocations in the gametes can lead to duplication or deletion of the chromosomal regions involved in the translocation. 45 Reduced fertility in translocation carriers may in part be the result of the requirement during meiosis for chromosomal translocations to form a quadrivalent or trivalent structure (reciprocal and Robertsonian translocations, respectively) to enable homologous chromosomes to pair. The formation of the quadrivalent or trivalent can lead to reduced fertility, firstly, due to the mechanics and time constraints to form such a structure 46 and secondly, as a result of the disjunction of the structures which is prone to produce genetically unbalanced gametes.…”