Optimal euploid embryo transfer strategy, fresh versus frozen, after preimplantation genetic screening with next generation sequencing: a randomized controlled trial.

OBJECTIVE: To compare two commonly used protocols (fresh vs. vitrified) used to transfer euploid blastocysts after IVF with preimplantation genetic screening. DESIGN: Randomized controlled trial. SETTING: Private assisted reproduction center. PATIENT(S): A total of 179 patients undergoing IVF treatment using preimplantation genetic screening. INTERVENTION(S): Patients were randomized at the time of hCG administration to either a freeze-all cycle or a fresh day 6 ET during the stimulated cycle. MAIN OUTCOME MEASURE(S): Implantation rates (sac/embryo transferred), ongoing pregnancy rates (PRs) (beyond 8 weeks), and live birth rate per ET in the primary transfer cycle. RESULT(S): Implantation rate per embryo transferred showed an improvement in the frozen group compared with the fresh group, but not significantly (75% vs. 67%). The ongoing PR (80% vs. 61%) and live birth rates (77% vs. 59%) were significantly higher in the frozen group compared with the fresh group. CONCLUSION(S): Either treatment protocol investigated in the present study can be a reasonable option for patients. Freezing all embryos allows for inclusion of all blastocysts in the cohort of embryos available for transfer, which also results in a higher proportion of patients reaching ET. These findings suggest a trend toward favoring the freeze-all option as a preferred transfer strategy when using known euploid embryos. CLINICAL TRIAL REGISTRATION NUMBER: NCT02000349.

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.

Validation of next-generation sequencing for comprehensive chromosome screening of embryos.

Massively parallel genome sequencing, also known as next-generation sequencing (NGS), is the latest approach for preimplantation genetic diagnosis. The purpose of this study was to determine whether NGS can accurately detect aneuploidy in human embryos. Low coverage genome sequencing was applied to trophectoderm biopsies of embryos at the blastocyst stage of development. Sensitivity and specificity of NGS was determined by comparison of results with a previously validated platform, array-comparative genomic hybridization (aCGH). In total, 156 samples (116 were blindly assessed) were tested: 40 samples were re-biopsies of blastocysts where the original biopsy specimen was previously tested for aCGH; four samples were re-biopsies of single blastomeres from embryos previously biopsied at the cleavage stage and tested using aCGH; 18 samples were single cells derived from well-characterized cell lines; 94 samples were whole-genome amplification products from embryo biopsies taken from previous preimplantation genetic screening cycles analysed using aCGH. Per embryo, NGS sensitivity was 100% (no false negatives), and 100% specificity (no false positives). Per chromosome, NGS concordance was 99.20%. With more improvement, NGS will allow the simultaneous diagnosis of single gene disorders and aneuploidy, and may have the potential to provide more detailed insight into other aspects of embryo viability.