Detection of aneuploidy and chromosomal mosaicism in human embryos during preimplantation sex determination by fluorescent in situ hybridisation, (FISH)

Abstract

Five couples at risk of producing offspring with X-linked recessive disease underwent in vitro fertilisation with a view to preimplantation determination of embryo sex and selective transfer of females. On day three postinsemination, one or two blastomeres were removed by embryo biopsy, and used for dual fluorescent in situ hybridisation with X and Y chromosome-specific DNA probes. In two cases, two female embryos were transferred and one pregnancy, (sex confirmed), is ongoing at 19 weeks. All eight embryos from one couple were of such poor quality that diagnosis was possible in one only. In the remaining two cases no embryos were transferred due to the detection of an abnormal number of X chromosome signals. Investigation of the biopsied embryos that were not transferred revealed evidence of mitotic non-disjunction in one and of complete X monosomy in a second. A surviving fetus with this latter constitution would have developed Turner syndrome and would also have been at high risk of X-linked disease. The use of fluorescent in situ hybridisation rather than the polymerase chain reaction allowed the detection of abnormal copy numbers of X chromosomes thus preventing the transfer of potentially abnormal zygotes.

Preimplantation Genetic Screening (PGS) with Comparative Genomic Hybridization (CGH) following day 3 single cell blastomere biopsy markedly improves IVF outcomes while lowering multiple pregnancies and miscarriages

“…Initial reports that aneuploidy employing FISH technology could be directly related to infertility were published in the early 1990s [5,16,23]. It is now accepted that the incidence of aneuploidy in embryos increases with maternal age [13].…”

Comparison of Aneuploidy Frequency to Sperm FISH and Sperm Apoptosis Results in Embryos That Lost the Vitality

“…Anöp lo i di nin ne de ni an ne ye bağ lı fak tör ler ola bile ce ği gi bi prob lem ba ba kay nak lı da ola bil mek tedir. 3,9,[29][30][31] Bu ça lış ma da, er ken dö nem de bu lu nan em bri yo lar da ge li şi min dur ma sı nı açık la ma ya ça-lış mak üze re em bri yo nun ken di sin de ve ba ba dan el de edi len sperm ler de araş tır ma plan lan mış tır.…”

Errors in Chromosome Segregation During Oogenesis and Early Embryogenesis

“…Although mosaicism in general is common in human embryos generated by IVF and increases with the number of days spent in culture, this almost universal aneuploid mosaicism is beyond what is normally seen in embryos from routine IVF patients ( [38][39][40][41][42] ).…”

“…Interphase FISH detection of the X and Y chromosomes for the purposes of embryo sexing first indicated that mosaicism is a common feature of human preimplantation embryos ( 38 ). Subsequent studies using autosomal probes for testing between three and nine chromosomes detected mosaic aneuploidy in more than half of the embryos investigated ( 39,41,42 ).…”