Multiple embryo manipulations in PGT-A cycles may result in inferior clinical outcomes.

RESEARCH QUESTION: Do embryos that undergo a thaw, biopsy and re-vitrification (TBR) for pre-implantation genetic testing for aneuploidy (PGT-A) have different ploidy and transfer outcomes compared with fresh biopsied embryos? DESIGN: Retrospective cohort study of all embryos that underwent the following procedures: fresh biopsy for PGT-A (fresh biopsy); embryos that were warmed, biopsied for PGT-A and re-vitrified (single biopsy TBR); embryos with a no signal result after initial biopsy that were subsequently warmed, biopsied and re-vitrified (double biopsy TBR). The patients who underwent transfers of those embryos at a single academic institution between March 2013 and December 2021 were also studied. RESULTS: About 30% of embryos planned for TBR underwent attrition. Euploidy rates were similar after biopsy: fresh biopsy (42.7%); single biopsy TBR (47.5%) (adjusted RR: 0.99, 0.88 to 1.12); and double biopsy TBR 50.3% (adjusted RR: 0.99, 0.80 to 1.21). Ongoing pregnancy over 8 weeks was not statistically significant (double biopsy TBR: 6/19 [31.6%] versus fresh biopsy: 650/1062 [61.2%]) (adjusted RR 0.52, 95% CI 0.26 to 1.03). The miscarriage rate increased (double biopsy TBR: 4/19 [21.1%] versus fresh biopsy: 66/1062 [6.2%])(RR 3.39, 95% CI 1.38 to 8.31). Live birth rate was also lower per transfer for the double biopsy TBR group (double biopsy TBR [18.75%] versus fresh biopsy [53.75%]) (RR 0.35, 95% CI 0.12 to 0.98), though not after adjustment (adjusted RR 0.37, 95% CI 0.13 to 1.09). These differences were not seen when single biopsy TBR embryos were transferred. CONCLUSIONS: Embryos that undergo TBR have an equivalent euploidy rate to fresh biopsied embryos. Despite that, double biopsy TBR embryos may have impaired transfer outcomes.

Reprogramming within hours following nuclear transfer into mouse but not human zygotes.

Fertilized mouse zygotes can reprogram somatic cells to a pluripotent state. Human zygotes might therefore be useful for producing patient-derived pluripotent stem cells. However, logistical, legal and social considerations have limited the availability of human eggs for research. Here we show that a significant number of normal fertilized eggs (zygotes) can be obtained for reprogramming studies. Using these zygotes, we found that when the zygotic genome was replaced with that of a somatic cell, development progressed normally throughout the cleavage stages, but then arrested before the morula stage. This arrest was associated with a failure to activate transcription in the transferred somatic genome. In contrast to human zygotes, mouse zygotes reprogrammed the somatic cell genome to a pluripotent state within hours after transfer. Our results suggest that there may be a previously unappreciated barrier to successful human nuclear transfer, and that future studies could focus on the requirements for genome activation.

The role of assisted reproductive technology in the management of recurrent pregnancy loss.

PURPOSE OF REVIEW: Description of genetic screening of preimplantation embryos as a means of reducing miscarriages in patients with recurrent pregnancy loss. RECENT FINDINGS: That the promise of preimplantation genetic screening (PGS) for ameliorating recurrent pregnancy loss has been fulfilled is controversial. An array of comparative studies has suggested a positive effect of PGS on implantation rate, but these have been balanced by studies showing no effect or a negative effect, highlighting the need for more rigorously designed studies and randomized controlled trials. Emerging technologies may provide more information from the embryo biopsies even as the mosaicism of the embryo and its implications for interpreting PGS data are recognized. SUMMARY: Through the screening of embryos for abnormality in chromosome number or structure and selecting only normal embryos for transfer, PGS was envisioned and applied as a therapeutic tool for improving implantation and live birth rates from in-vitro fertilization and providing a means of attenuating pregnancy loss in recurrent pregnancy loss patients. An array of reports on the effects of PGS on embryo implantation and live birth rates has been made since its introduction, showing, variously, increases, decreases or no changes in these parameters. Various factors may influence the efficacy of PGS, including the patient population to which it is applied, technical aspects such as embryo biopsy, the genetic analysis and embryo culture environment, the current limitation of the genetic analysis (a subset of, rather than all, the 24 chromosomes) and the mosaicism of the embryo and blastocyst. Collectively, these contribute to the challenge of optimizing PGS and understanding how the screening result reflects the ultimate genetic constitution of the conceptus. Emerging cytogenetic and molecular technologies such as comparative genomic hybridization and microarray analysis may provide a broader appraisal of the embryo for a more comprehensive evaluation of developmental potential and prognosis for live birth.