Faculty Bibliography

OBJECTIVE:To assess patient decisions regarding mosaic embryos and their impact on clinical outcomes. DESIGN/METHODS:Review of patients who had genetic counseling regarding mosaic embryos. SETTING/METHODS:Academic department. PATIENT(S)/METHODS:Ninety-eight patients who had mosaic embryos but no euploid embryos. INTERVENTION(S)/METHODS:Genetic counseling to discuss mosaic-embryo transfer (MET) after preimplantation genetic testing for aneuploidy. MAIN OUTCOME MEASURE(S)/METHODS:Patient decisions regarding MET. Outcomes for patients who pursued MET were compared with those for patients who pursued additional in vitro fertilization or intrauterine insemination cycles. Decisions regarding prenatal testing after MET were assessed. RESULT(S)/RESULTS:Initially, 29.6% of patients pursued MET and 41.8% attempted a new treatment cycle. Only 6.1% of patients discarded their mosaic embryos without further treatment. Of the remaining patients, 2.0% transported their mosaic embryos to a different facility and 20.5% had not taken further action while their embryos remain stored. Patients who pursued additional cycles were more likely to have an ongoing pregnancy compared with those who pursued MET (51.2% vs. 27.6%; P<.05); however, there was no statistically significant difference in the percentage of patients who had at least one biochemical pregnancy or spontaneous abortion. Ultimately, 32.7% of patients underwent MET, and 54.5% of pregnant patients pursued amniocentesis. CONCLUSION(S)/CONCLUSIONS:MET is desired by a substantial proportion of patients who do not have euploid embryos. Patients who opt for additional treatment cycles have a greater chance of achieving an ongoing pregnancy compared with those who pursue MET; however, future studies are needed to compare the cost-effectiveness for both options.

Two of the many milestone developments in the field of assisted reproduction have been oocyte donation and preimplantation genetic testing for aneuploidy (PGT-A). Because it has been demonstrated that even young women produce a meaningful proportion of aneuploid embryos, screening out such abnormalities could potentially increase the efficacy of donor egg (DE) cycles. In this retrospective cohort study, we investigated the effect of PGT-A on DE cycle outcomes, including implantation rate (IR), spontaneous abortion rate (SABR), and ongoing pregnancy/live birth rate. We used fresh and frozen donor cycles not using PGT-A as comparison groups; all cases involved single embryo transfer. Data analysis revealed that PGT-A did not improve pregnancy outcome metrics in DE cycles, although there was a trend toward decreasing the SABR. There was a significant increase in IR with fresh cycles outperforming all frozen cycles. Overall, these results suggest that the benefits of performing PGT-A on embryos derived from young DEs may be limited and that there is an effect of the freezing process on pregnancy outcomes. These findings may provide useful insights into the science and practice of PGT-A across all of its applications.

Aneuploid conceptions constitute the majority of pregnancy failures in women of advanced maternal age. The best way to combat age-related decline in fertility is through preimplantation genetic testing for aneuploidy (PGT-A). PGT-A allows for better embryo selection, which improves implantation rates with single embryo transfer and reduces miscarriage rates. Single embryo transfers decrease multiple gestations and adverse pregnancy outcomes such as preterm or low birth weight infants. Advancements in extended embryo culture, blastocyst biopsy techniques, and 24-chromosome aneuploidy screening platforms have made PGT-A safe and accessible for all patients who undergo in vitro fertilization. Improved genomic coverage of new sequencing platforms, such as next-generation sequencing, has increased the identification and diagnosis of mosaicism and partial aneuploidies in preimplantation embryos. Mosaic embryos have decreased viability compared to euploid embryos when transferred, but some mosaic embryos result in normal live births. Whole genome amplification artifacts may contribute to a misdiagnosis of mosaicism, or some mosaic embryos may self-correct to euploid after implantation. For this reason, patients without euploid embryos should be given the option of transferring mosaic embryos after genetic counseling. Further research is needed to characterize which mosaic embryos may be viable.

Uroplakin (UP) tetraspanins and their associated proteins are major mammalian urothelial differentiation products that form unique 2D-crystals of 16-nm particles ("urothelial plaques") covering the apical urothelial surface. Although uroplakins are highly expressed only in mouse urothelium and are often referred to as being urothelium-specific, they are also expressed in several nonurothelial cell types in stomach, kidney, prostate, epididymis, testis/sperms and ovary/oocytes. In oocytes, uroplakins co-localize with CD9 on cell surface and multivesicular body-derived exosomes, and the cytoplasmic tail of UPIIIa undergoes a conserved fertilization-dependent, Fyn-mediated tyrosine-phosphorylation that also occurs in Xenopus laevis eggs. Uroplakin knockout and antibody blocking reduce mouse eggs' fertilization rate in in vitro fertilization assays, and UPII/IIIa double-knockout mice have a smaller litter size. Phylogenetic analyses showed that uroplakin sequences underwent significant mammal-specific changes. These results suggest that, by mediating signal transduction and modulating membrane stability that do not require 2D-crystal formation, uroplakins can perform conserved and more ancestral fertilization functions in mouse and frog eggs. Uroplakins acquired the ability to form 2D- crystalline plaques during mammalian divergence enabling them to perform additional functions, including umbrella cell enlargement and the formation of permeability and mechanical barriers, in order to protect/modify the apical surface of the modern-day mammalian urothelium.