Differences in pregnancy outcomes in donor egg frozen embryo transfer (FET) cycles following preimplantation genetic screening (PGS): a single center retrospective study

PURPOSE: This study aims to test the hypothesis, in a single-center retrospective analysis, that live birth rates are significantly different when utilizing preimplantation genetic screening (PGS) compared to not utilizing PGS in frozen–thawed embryo transfers in our patients that use eggs from young, anonymous donors. The question therefore arises of whether PGS is an appropriate intervention for donor egg cycles. METHODS: Live birth rates per cycle and live birth rates per embryo transferred after 398 frozen embryo transfer (FET) cycles were examined from patients who elected to have PGS compared to those who did not. Blastocysts derived from donor eggs underwent trophectoderm biopsy and were tested for aneuploidy using array comparative genomic hybridization (aCGH) or next-generation sequencing (NGS), then vitrified for future use (test) or were vitrified untested (control). Embryos were subsequently warmed and transferred into a recipient or gestational carrier uterus. Data was analyzed separately for single embryo transfer (SET), double embryo transfer (DET), and for own recipient uterus and gestational carrier (GC) uterus recipients. RESULTS: Rates of implantation of embryos leading to a live birth were significantly higher in the PGS groups transferring two embryos (DET) compared to the no PGS group (GC, 72 vs. 56 %; own uterus, 60 vs. 36 %). The live birth implantation rate in the own uterus group for SET was higher in the PGS group compared to the control (58 vs. 36 %), and this almost reached significance but the live birth implantation rate for the SET GC group remained the same for both tested and untested embryos. Live births per cycle were nominally higher in the PGS GC DET and own uterus SET and DET groups compared to the non-PGS embryo transfers. These differences almost reached significance. The live birth rate per cycle in the SET GC group was almost identical. CONCLUSIONS: Significant differences were noted only for DET; however, benefits need to be balanced against risks associated with multiple pregnancies. Results observed for SET need to be confirmed on larger series and with randomized cohorts

Continuing to deliver: the evidence base for pre-implantation genetic screening

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Chromosomal Rainbows detect Oncogenic Rearrangements of Signaling Molecules in Thyroid Tumors

Altered signal transduction can be considered a hallmark of many solid tumors. In thyroid cancers the receptor tyrosine kinase (rtk) genes NTRK1 (Online Mendelian Inheritance in Man = OMIM *191315, also known as 'TRKA'), RET ('Rearranged during Transfection protooncogene', OMIM *164761) and MET (OMIM *164860) have been reported as activated, rearranged or overexpressed. In many cases, a combination of cytogenetic and molecular techniques allows elucidation of cellular changes that initiate tumor development and progression. While the mechanisms leading to overexpression of the rtk MET gene remain largely unknown, a variety of chromosomal rearrangements of the RET or NTKR1 gene could be demonstrated in thyroid cancer. Abnormal expressions in these tumors seem to follow a similar pattern: the rearrangement translocates the 3'-end of the rtk gene including the entire catalytic domain to an expressed gene leading to a chimeric RNA and protein with kinase activity. Our research was prompted by an increasing number of reports describing translocations involving ret and previously unknown translocation partners. We developed a high resolution technique based on fluorescence in situ hybridization (FISH) to allow rapid screening for cytogenetic rearrangements which complements conventional chromosome banding analysis. Our technique applies simultaneous hybridization of numerous probes labeled with different reporter molecules which are distributed along the target chromosome allowing the detection of cytogenetic changes at near megabase-pair (Mbp) resolution. Here, we report our results using a probe set specific for human chromosome 10, which is altered in a significant portion of human thyroid cancers (TC's). While rendering accurate information about the cytogenetic location of rearranged elements, our multi-locus, multi-color analysis was developed primarily to overcome limitations of whole chromosome painting (WCP) and chromosome banding techniques for fine mapping of breakpoints in papillary thyroid cancer (PTC)

Chromosomal Rainbows detect Oncogenic Rearrangements of Signaling Molecules in Thyroid Tumors

Altered signal transduction can be considered a hallmark of many solid tumors. In thyroid cancers the receptor tyrosine kinase (rtk) genes NTRK1 (Online Mendelian Inheritance in Man = OMIM *191315, also known as 'TRKA'), RET ('Rearranged during Transfection protooncogene', OMIM *164761) and MET (OMIM *164860) have been reported as activated, rearranged or overexpressed. In many cases, a combination of cytogenetic and molecular techniques allows elucidation of cellular changes that initiate tumor development and progression. While the mechanisms leading to overexpression of the rtk MET gene remain largely unknown, a variety of chromosomal rearrangements of the RET or NTKR1 gene could be demonstrated in thyroid cancer. Abnormal expressions in these tumors seem to follow a similar pattern: the rearrangement translocates the 3'-end of the rtk gene including the entire catalytic domain to an expressed gene leading to a chimeric RNA and protein with kinase activity. Our research was prompted by an increasing number of reports describing translocations involving ret and previously unknown translocation partners. We developed a high resolution technique based on fluorescence in situ hybridization (FISH) to allow rapid screening for cytogenetic rearrangements which complements conventional chromosome banding analysis. Our technique applies simultaneous hybridization of numerous probes labeled with different reporter molecules which are distributed along the target chromosome allowing the detection of cytogenetic changes at near megabase-pair (Mbp) resolution. Here, we report our results using a probe set specific for human chromosome 10, which is altered in a significant portion of human thyroid cancers (TC's). While rendering accurate information about the cytogenetic location of rearranged elements, our multi-locus, multi-color analysis was developed primarily to overcome limitations of whole chromosome painting (WCP) and chromosome banding techniques for fine mapping of breakpoints in papillary thyroid cancer (PTC)