Benefits and drawbacks of preimplantation genetic diagnosis (PGD) for reciprocal translocations: lessons from a prospective cohort study

Abstract

Preimplantation genetic diagnosis (PGD) using fluorescence in situ hybridisation probes was carried out for 59 couples carrying reciprocal translocations. Before treatment, 85% of pregnancies had resulted in spontaneous miscarriage and five couples had achieved a healthy live-birth delivery. Following treatment, 33% of pregnancies failed and 21of 59 couples had a healthy live-born child. The accuracy of diagnosis was 92% (8% false abnormal and 0% false normal results). The overall incidence of 2:2 alternate segregation products was 44%; however, products consistent with 2:2 adjacent segregation were Btwice as likely from male heterozygotes, and those with 3:1 disjunction were three times more likely from female heterozygotes. Our results indicate that up to three stimulation cycles per couple would give an B50% chance of a successful live birth, with the risk of miscarriage reduced to the level found in the general population. In our study, 87% of all normal/balanced embryos available were identified as being suitable for transfer. We conclude that PGD provides benefit for couples with high-risk translocations by reducing the risk of miscarriage and avoiding a pregnancy with an unbalanced form of the translocation; however, for fertile carriers of translocations with a low risk of conceiving a chromosomally unbalanced offspring, natural conception may be a more viable option.

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

“…In view of poorer assisted reproductive technology outcome in RCP and RT patients and slower growth profile of the embryos obtained from the translocation carriers [20], the number of biopsy acceptable embryos seems to be satisfying. However, we observed low percentage of transferable embryos (19.4%), which confirms observations of other authors [7,14,16,22]. Moreover, the European Society for Human Reproduction and Embryology (ESHRE) PGD Consortium released data collection X (2010) where they detailed the PGD results of 57 participating centers [23].…”

“…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].…”

“…Theoretically, chance of producing normal or balanced gametes is 4:32 for RCP translocation, and 4:16 for RT translocations. However, the actual percentage depends on several factors, including chromosomes involved, the breakpoints, and carrier's gender [6,7]. It should be noted that levels of unbalanced gametes will be significantly higher than the empiric risk of having a chromosomally unbalanced live birth.…”

Chromosomal analysis of blastocysts from balanced chromosomal rearrangement carriers

“…However, in one study, blastocyst-stage embryos previously analyzed by array CGH were reanalyzed by FISH with remarkably consistent results , indicating that technical constraints of FISH are not solely responsible for the observed incongruence between cleavage-stage and blastocyst chromosomal composition. In addition, FISH-based PGD benefits CR carriers with improved pregnancy outcomes, which provide clinical evidence for the efficacy of FISH (Scriven et al 2013). Nonetheless, cleavage-stage FISH is not the ideal PGD protocol for CR carriers, given that a significant proportion of embryos exhibiting balanced composition of chromosomes involved in CR had abnormalities in other chromosomes.…”

PGD management scheme for older females with balanced translocations: Do older females have less chance of balanced embryo transfer?

“…With the use of array-based comparative genomic hybridization (aCGH), translocation as well as aneuploid embryos would have been detected. However, FISH is still widely used to detect translocations (19,20). This is mostly due to the size of breakpoints involved in translocation because in some cases, even the high-resolution aCGH cannot detect the translocated segment (21).…”