Faculty Bibliography

OBJECTIVE: There has been a steady rise in the use of donor gametes in assisted reproductive technology (ART); however, recommendations regarding genetic screening of donors are still limited and based on the donors' reported ethnicities. In contrast, pan-ethnic carrier screening is routinely offered to fertility patients across the US under the guidance of medical society recommendations. This discrepancy in screening practices may result in patients receiving donor gametes which confer a high reproductive risk. Screening donors and patients for the same genetic conditions will allow patients planning to use donor gametes to make the most informed decisions throughout the IVF process. We sought to examine if there are remarkable differences in the carrier frequencies of genetic diseases between general fertility patients and gamete donors. DESIGN: Retrospective. MATERIALS AND METHODS: We calculated and compared the observed carrier frequencies of various genetic diseases in our general fertility population and our gamete donor population in order to identify any similarities or differences. Data was included from research-consenting patients tested for 200+ autosomal recessive and X-linked conditions over the last 3 years. To account for ethnicity, only individuals who self-reported being of European descent were included. The study population thus included 643 gamete donors and 6,248 general fertility patients (non-donors). RESULTS: We calculated and compared the observed carrier frequencies of select high-impact conditions in our donor and non-donor patient populations. No significant differences in carrier rates between the two populations were observed. For example, donors and non-donors were carriers of Smith-Lemli-Opitz Syndrome at a frequency of 1/58 and 1/53, respectively. For Glycogen Storage Disease (Type II), respective carrier frequencies for donors and non-donors were 1/80 and 1/86. A similarity in frequency was also seen in Nonsyndromic Hearing Loss & Deafness (GJB2 related), with rates of 1/21 (donors) and 1/18 (non-donors). CONCLUSIONS: These results show that, as predicted, gamete donors are equally as likely to be carriers as general fertility patients. Knowing this, the greatest reduction in risk for those receiving donated gametes will come from ensuring both donor and patient undergo similar levels of carrier screening. It will be important to ensure that the manner in which screening is conducted does not unnecessarily eliminate healthy carriers from the donation process

OBJECTIVE: Preimplantation Genetic Diagnosis (PGD) has helped couples avoid inherited genetic diseases for over 25 years. Karyomapping can streamline this process with a high resolution and rapid result test design. This study is an evaluation of the Single Nucleotide Polymorphism (SNP)- based karyomapping platform as the best standard for preimplantation genetic diagnosis of single gene disorders, using an analysis of over 9,000 trophectoderm biopsies and 304 diverse genetic conditions. DESIGN: Retrospective, multi-faceted analysis of embryo biopsies submitted for single-gene diagnosis on the new karyomapping test platform. MATERIALS AND METHODS: Familial DNA from either buccal swabs or blood samples was analyzed along with amplified embryo DNA using the Illumina Karyomapping assay. The data was analyzed with BlueFuse Multi software to detect affected familial haplotypes and determine disease status of embryos. When requested, aneuploidy screening was performed in parallel using either Comparative Genomic Hybridization microarray (aCGH) or Next Generation Sequencing. RESULTS: 1,417 families were analyzed using the karyomapping technology, with an average PGD probe design length of 4 weeks. In total, 9,426 blastocyst biopsies were assessed, averaging 6.8 samples per couple. Of the samples tested, 4.8% were given a "no result" diagnosis because quality control metrics were not met, or the sample had poor amplification. 1.4% were given a "no diagnosis" or "inconclusive" result due to sample contamination or partial/incomplete results. The remaining 8,848 biopsies (93.9%) were successfully diagnosed for 304 different genetic conditions. Karyomapping alone was performed on 294 cases (2,013 samples), resulting in a transfer rate (proportion of assessed embryos available for transfer) of 46.7%. Aneuploidy screening was included in the remaining 1,123 cases, resulting in a transfer rate of 29.9%. CONCLUSIONS: Karyomapping has proven to be a reliable and reproducible test, as evidenced by the robust diagnosis of 93.9% of the 9,426 biopsies analyzed over the course of 2 years. With karyomapping, the vast number of data points available across the entire genome allows for diagnosis of common, uncommon, and novel genetic disorders with a single standard test platform. This is in stark contrast to the time-consuming customization required by the previous methodology using short tandem repeats. The families undergoing PGD are benefiting from this technology, particularly those in need of a rapid test design. Great success with this technology demonstrates that karyomapping has become the new gold standard for PGD

BACKGROUND: Preimplantation genetic screening (PGS) affords couples the knowledge of embryo ploidy status prior to embryo transfer (ET). Many patients arrive at donor egg (DE) after multiple failed autologous in vitro fertilization (IVF) cycles, of which many may be due to aneuploidy. Our goal was to assess if knowledge of ploidy status decreases disposition time to DE and, ultimately, live birth (LB). OBJECTIVE: To determine if patient knowledge of embryo ploidy status through use of PGS using array comparative genomic hybridization (aCGH) changes disposition time DE enrollment at a large university-based fertility center. MATERIALSAND METHODS: Patients who enrolled in the DE program between 2011 and 2014 at the NYU Fertility Center that had a prior in vitro fertilization (IVF) cycle were identified. The number of IVF egg retrievals (ER) and ET with and without PGS performed before enrolling in DE were collected. The primary outcome was time in months from initial consultation visit to first DE transfer and to live birth. If the patient had a prior LB, the consultation visit was the first visit after the LB to discuss continued childbearing. Unpaired t-tests and chi-square were used for analysis with p< 0.05 defined as significance. RESULTS: A total of 110 patients had both IVF and DE cycles at NYUFC. There were 9 patients that underwent day 3 embryo biopsy and PGS with aCGH and 19 patients that had previously undergone trophectoderm biopsy and PGS with aCGH. Of these patients that did PGS, only 7/28 (25%) made at least one euploid embryo. Use of PGS did not decrease the number of IVF cycles, disposition time to DE, or time to DE LB. Prior parity and pregnancy rates were similar in both groups. CONCLUSIONS: One might expect that knowledge of embryo aneuploidy would affect disposition time to DE. This small retrospective cohort study shows no difference in disposition time to DE. However, given that trophectoderm biopsy with aCGH is a relatively new technology, it may be too early to assess the true impact on knowledge of ploidy status on disposition to DE (Figure Presented)

OBJECTIVE: To determine the relationship between blastocyst growth parameters and birth weight. DESIGN: Cohort study. SETTING: University-affiliated fertility center. PATIENT(S): In vitro patients who delivered a singleton after a single-blastocyst transfer. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Birth weight adjusted for gestational age at delivery and gender, with adjusted birth weight examined for association with blastocyst scores and grades. RESULT(S): After standard in vitro fertilization (IVF) and thawed embryo transfers, greater birth weight was associated with a higher inner cell mass grade. The grade of the trophectoderm and stage of the blastocyst did not relate to weight. CONCLUSION(S): Embryonic growth as early as day 5 can predict the progress of fetal development as measured by birth weight.