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

Scriven, Paul N.; Flinter, Frances; Khalaf, Yakoub; Lashwood, Alison; Ogilvie, Caroline Mackie

doi:10.1038/ejhg.2013.9

Cited by 51 publications

(54 citation statements)

References 41 publications

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“…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].…”

Section: Discussionsupporting

confidence: 74%

“…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].…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Liss¹,

Kiewisz

Zabielska

et al. 2015

Folia Histochem Cytobiol.

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Introduction. Carriers of reciprocal (RCP) and Robertsonian (RT) translocations are known to be at risk for reproductive difficulties. Preimplantation genetic diagnosis (PGD) is one of the options these carriers have to try to fulfill their desire to have a child. The FISH technique is one of the best method to detect RCPs, and, together with the Next Generation Sequencing, to diagnose RTs. The aim of the present study was to assess the usefulness of the FISH method for rapid diagnosis of translocations in our center to improve the reproductive counseling. Material and methods. From 2008 to 2012 one hundred and twenty seven fresh cycles of the in vitro fertilization (IVF; without freezing embryos) were performed in 42 couples with an RCP and 35 couples with an RT translocations. The patients were diagnosed before IVF as translocation carriers and therefore they opted for PGD. The classical FISH protocol has been applied with specific oligonucleotide probes. Results.In total 521 blastomeres were tested in order to determine the presence or absence of genetic anomalies resulting from one of the parents being a translocation carrier. Despite the large number of abnormal embryos (407 embryos -78.1% of all examined embryos), 19.4% of blastomeres appeared to come from a normal or balanced embryos that may have been transferred to the uterus. In 63 of the 127 cycles embryo transfer (ET) was feasible and 24 women had a successful singleton or twin pregnancy. Thus, a live delivery rate of 18.9% per started cycles and 38.1% per cycle with ET was obtained. Conclusion. FISH should be regarded as an optimal preimplantation genetic diagnosis method for specific RCP and RT translocation carriers to increase the chance of successful IVF procedure.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Liss¹,

Kiewisz

Zabielska

et al. 2015

Folia Histochem Cytobiol.

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“…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.…”

Section: Discussionmentioning

confidence: 99%

Chromosomal analysis of blastocysts from balanced chromosomal rearrangement carriers

Gui

Yao

et al. 2016

Reproduction

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Balanced chromosomal rearrangements (CRs) are among the most common genetic abnormalities in humans. In the present study, we have investigated the degree of consistency between the chromosomal composition of the blastocyst inner cell mass (ICM) and trophectoderm (TE) in carriers with balanced CR, which has not been previously addressed. As a secondary aim, we have also evaluated the validity of cleavage-stage preimplantation genetic diagnosis (PGD) based on fluorescence in situ hybridization (FISH) of blastocysts from CR carriers. Blastocyst ICM and TE were screened for chromosomal aneuploidy and imbalance of CR-associated chromosomes based on whole-genome copy number variation analysis by low-coverage next-generation sequencing (NGS) following single-cell wholegenome amplification by multiple annealing and looping-based amplification cycling. The NGS results were analyzed without knowledge of cleavage-stage FISH results. NGS results for blastocyst ICM and TE from CR carriers were 86.49% (32/37) consistent. Of the 1702 (37!46) chromosomes examined, 99.47% (1693/1702) showed consistency. However, only 40.0% (18/45) of all embryos had consistent results for chromosomes involved in CR, as determined by blastocyst NGS and cleavage-stage FISH. Of the 85 CR-affected chromosomes analyzed by FISH, 37.65% (32/85) were incongruous with NGS results, with 87.5% (28/32) showing imbalanced composition by FISH but balanced composition by NGS. These results indicate that chromosomal composition of blastocyst ICM and TE in balanced CR carriers is highly consistent, and that PGD based on cleavage-stage FISH is inaccurate; therefore, using blastocyst TE biopsies for NGS-based PGD is recommended for identifying chromosomal imbalance in embryos from balanced CR carriers.

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“…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).…”

Section: Discussionmentioning

confidence: 99%

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

Tulay

Gültomruk²,

Fındıklı³

et al. 2016

J Turkish German Gynecol Assoc

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Patient informationTranslocation carriers were subdivided according to maternal age (<35 years and advanced maternal age of ≥35 years) and translocation type, i.e., reciprocal and Robertsonian. A total of 20 couples with maternal ages of <35 years with 37 PGD cycles were analyzed within the reciprocal translocation carrier group. The advanced maternal age group of reciproObjective: Carriers of reciprocal and Robertsonian translocations have a higher risk of experiencing infertility and repeated miscarriages. It is well established that with advancing maternal age, the risk of aneuploidies in embryos increases. In this study, the chance of developing balanced embryos in translocation carriers with advanced maternal age was analyzed to establish a management scheme for couples seeking fertility treatment and preimplantation genetic diagnosis (PGD). Material and Methods:Biopsy was performed on cleavage-stage embryos. Multicolor fluorescence in situ hybridization was used for PGD.The translocation carriers underwent a total of 55 cycles of PGD. Genetics diagnosis and cycle outcomes of PGD cases were examined.Results: This study showed that the chance of obtaining a balanced embryo from the Robertsonian translocation carriers was significantly less when the maternal age is advanced. Similar rates for balanced embryos were obtained from the reciprocal translocation carriers. Conclusion:The results of this study show that maternal age plays an important role and that genetic counselling and planning for a PGD cycle in translocation carriers, particularly for Robertsonian carriers, must be accordingly adapted. (J Turk Ger Gynecol Assoc 2016; 17: 91-5) Keywords: PGD, maternal

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

Cited by 51 publications

References 41 publications

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

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

Chromosomal analysis of blastocysts from balanced chromosomal rearrangement carriers

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

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