45,X product of conception after preimplantation genetic diagnosis and euploid embryo transfer: evidence of a spontaneous conception confirmed by DNA fingerprinting

Abstract

BackgroundPreimplantation genetic screening (PGS) provides an opportunity to eliminate a potential implantation failure due to aneuploidy in infertile couples. Some studies clearly show that twins following single embryo transfer (SET) can be the result of a concurrent natural conception and an incidence as high as 1 in 5 twins has been reported.In our case PGS was performed on trophectoderm (TE) biopsies by quantitative polymerase chain reaction (qPCR). The product of conception (POC) was cytogenetically investigated after selection of the placental villi by means of the direct method. Molecular cytogenetic characterization of the POC was performed by fluorescence in situ hybridization (FISH) and array-comparative genomic hybridization (a-CGH) analyses. To investigate the possibility of a spontaneous conception, a panel of 40 single nucleotide polymorphisms (SNPs) was used to compare genetic similarity between the DNA of the POC and the DNA leftover of the TE biopsy.FindingsWe describe a 36-year old infertile woman undergoing PGS who had a spontaneous abortion after a single euploid embryo transfer on a spontaneous cycle. The POC showed a 45,X karyotype confirmed by FISH and a-CGH. DNA fingerprinting demonstrated a genetic similarity of 75 % between the DNA of the POC and TE biopsy, consistent with a sibling status. All supernumerary euploid embryos were also tested showing a non-self relationship with the POC, excluding a mix-up event at the time of fetal embryo transfer.ConclusionsDNA fingerprinting of the transferred blastocyst and POC, confirmed the occurrence of a spontaneous conception. This case challenges the assumption that a pregnancy after assisted reproductive technology (ART) is always a result of ART, and strengthens the importance to avoid intercourses during PGS and natural transfer cycles. Moreover, cytogenetic analysis of the POCs is strongly recommended along with fingerprinting children born after PGS to see what the concordance is between the embryo transferred and the resultant child.

Dichorionic diamniotic twin pregnancy after preimplantation genetic testing and single blastocyst transfer

“…Cases of life‐threatening complications, such as ruptured heterotopic pregnancy as a consequence of spontaneous pregnancy after sexual intercourse during single embryo transfer in the natural cycle, have been reported (Aoki et al, 2017; Yoder et al, 2016). Moreover, in cases where PGT is desired, there is a risk of clinically severe genetic anomalies when natural conceptions are involved (Bettio et al, 2016). Therefore, the potential risks of intercourse during IVF treatment should be weighed against the benefits.…”

Preimplantation genetic testing as a component of root cause analysis of errors and reassignment of embryos in IVF

“…This could result in an unexpectedly affected offspring. A case of this has been described by Bettio and colleagues, where a 45,X result was found for products of conception after a spontaneous abortion in a patient undergoing PGT for aneuploidies (Bettio et al, 2016). DNA fingerprinting was performed on the products of conception and euploid IVF embryos using 40 SNP, with results showing a similarity rate for the products of conception that was consistent with sibling and non-self relationship.…”