Faculty Bibliography

OBJECTIVE: To compare cycle and clinical outcomes between natural or medicated FET cycles. DESIGN: Retrospective study in an academic institution. MATERIALS AND METHODS: There were 1177 FET cycles from 2005- 2012. FET included embryos created from autologous or donor oocytes. Embryo transfers from oocyte thaws were excluded. Groups were analyzed for % donor cycles, % vitrification, % preimplantation genetic diagnosis/ screening (PGD), number of monitoring days, embryos transferred (ET), embryos thawed, day of embryo transfer, maximal endometrial (EM) thickness before transfer, peak estradiol (E2) and progesterone (P4) in follicular cycle, clinical pregnancy rate (CPR), spontaneous abortion rate (SABR) and ongoing/live birth rate (OP/LBR). CPR was defined by fetal cardiac activity on 1st-trimester ultrasound. SABR was calculated per pregnancy with a sac. T-tests were performed with p<0.05. RESULTS: Subset analysis was performed excluding PGD cycles, confirming no difference between natural and medicated cycles except for days of monitoring, peak E2 and peak P4. CONCLUSION: There can be advantages to both natural FET (lack of medication costs and injections) and medicated cycles (flexibility). Natural and medicated FET are equally effective in terms of pregnancy outcomes and should be offered based on patient preference and suitability (Table Presented)

OBJECTIVE: Advancements in genomics allow for expanded, cost-effective, and high-throughput carrier screening. The American College of Medical Genetics (ACMG) recommends that phenotype and penetrance should be considered in selecting diseases for inclusion. Based on 1000 clinical samples screened, the selected diseases were classified according to these factors with the goal of improving transparency, pre- and post-test counseling and results disclosure protocols. DESIGN: Retrospective study. MATERIALS AND METHODS: Recombine's Comprehensive Carrier Screen for 978 mutations associated with 181 recessive diseases was performed on 1000 clinical referrals. Diseases were classified into 2 groups: high impact (significant effect on quality of life/reduced lifespan) and variable spectrum (less severe phenotype/lower penetrance). Informed consent to utilize de-identified data was obtained from all patients. RESULTS: See table (Table Presented) CONCLUSION:With the full panel, ~99% of patients carry at least 1 mutation. More than 50% of samples carry MTHFR mutations. Considering only high-impact diseases, ~40% of patients carry at least 1 mutation. Inclusion of mild disorders may create anxiety and logistical concerns for patients and physicians. This anxiety can be reduced with post-test genetic counseling, transparency about differences in severity between high-impact and variable spectrum diseases in all materials (pre-counseling, web-based & reports), and the ability to customize the disease panel

PURPOSE: The objective of our study was to determine if trophectoderm biopsy, vitrification, array-comparative genomic hybridization and single thawed euploid embryo transfer (STEET) can reduce multiple gestations and yield high pregnancy and low miscarriage rates. METHODS: We performed a retrospective observational study comparing single thawed euploid embryo to routine age matched in vitro fertilization (IVF) patients that underwent blastocyst transfer from 2008 to 2011 and to our best prognosis group donor oocyte recipients (Donor). Our main outcome measures were implantation rate, clinical pregnancy rate, spontaneous abortion rate and multiple gestation rate. RESULTS: The STEET group had a significantly higher implantation rate (58 %, 53/91) than the routine IVF group (39 %, 237/613) while the Donor group (57 %, 387/684) had a similar implantation rate. The clinical pregnancy rates were not statistically different between the STEET and IVF groups. However, the multiple gestation rate was significantly lower in the STEET group (STEET 2 % versus IVF 34 %, Donor 47 %). CONCLUSIONS: STEET results in a high pregnancy rate, low multiple gestation rate and miscarriage rates. Despite the older age of STEET patients and transfer of twice as many embryos, the implantation rate for STEET was indistinguishable from that for egg donation. STEET offers an improvement to IVF, lowering risks without compromising pregnancy rate.

Objective: Next generation sequencing (NGS), a class of methods involving the production of vast quantities of DNA sequence data, is revolutionising genetic diagnostics. However, NGS has not been applied to research or diagnostics involving human embryos due to technical obstacles that prevent analysis single cells. We aimed to create new methods overcoming these limitations, allowing clinical application of NGS technology for the identification of viable/ healthy embryos. Methods: Whole genome amplification and NGS (Ion Torrent) methods were optimised. Data was analysed with novel tools developed by our laboratory. Results: In pre-clinical work, NGS correctly diagnosed abnormalities in 100% of single cells isolated from aneuploid cell lines. Additionally, 45/45 aneuploid embryos donated for research were also successfully diagnosed (verified by blinded analysis using arrayCGH). NGS accurately detected single gene disorders, correctly diagnosing cystic fibrosis in single cells from an affected individual. Moreover, a mitochondrial DNA mutation was successfully detected and accurately quantified in single fibroblasts from a heteroplasmic patient with mitochondrial disease. Ultimately, NGS was employed clinically for the purpose of selecting chromosomally normal blastocysts for uterine transfer, resulting in a pregnancy. Conclusions: A powerful NGS technique applicable to single cells was successfully developed, allowing simultaneous testing for aneuploidy, single gene mutations and mitochondrial disease with exceptional accuracy. NGS also provided a DNA fingerprint for the sample, assisting embryo identification. It was possible to complete NGS analysis in a timescale compatible with a fresh embryo transfer. Furthermore, the cost was significantly less than existing methods for embryo testing, suggesting this approach may ultimately bring preimplantation diagnosis for serious genetic disorders within the reach of a much larger number of patients. Following rigorous pre-clinical validation, the novel protocol was applied clinically, resulting in a healthy ongoing pregnancy. This represents the first report detailing a pregnancy achieved after using an NGS-based embryo screening protocol