Faculty Bibliography

Although controversial, increasing paternal age has been shown to negatively affect assisted reproductive technology (ART) outcomes and success rates. Most studies investigating the effect of paternal age on ART outcomes use a donor oocyte model to minimize maternal aneuploidy contribution. This study sought to determine whether increasing paternal age is associated with adverse in vitro fertilization (IVF) outcomes when aneuploidy is minimized using preimplantation genetic screening. There were 573 single thawed euploid embryo transfers from 473 patients undergoing oocyte donor and autologous IVF cycles. Cycles were categorized according to paternal age at oocyte retrieval, and an age adjustment was performed for maternal age in order to evaluate for an isolated paternal age effect. Fertilization rate was found to decrease significantly with increasing paternal age ( P = .04). After controlling for oocyte age, there was no significant difference in pregnancy outcomes across all paternal age categories after euploid embryo transfer, including implantation rate ( P = .23), clinical pregnancy rate ( P = .51), and spontaneous abortion rate ( P = .55). Therefore, if a couple is able to produce and transfer a single thawed euploid embryo, no difference in IVF pregnancy outcomes is identified with increasing paternal age.

PURPOSE: The aim of this study was to report the results of IVF with trophectoderm biopsy and preimplantation genetic screening (PGS) following delayed intracytoplasmic sperm injection (ICSI). METHODS: Patients undergoing IVF with PGS and delayed ICSI were included in the study. Indications for delayed ICSI included absent or poor fertilization via standard insemination or more than 50 % immature oocytes, noted post-cumulus stripping for standard ICSI procedure. Delayed ICSI was performed the day after retrieval due to absent or poor fertilization. The immature oocytes were kept in extended culture, and if demonstrated maturity, ICSI was performed. Primary outcome included fertilization rate and blastocyst stage formation, defined by the number of blastocysts for biopsy. Secondary outcome included aneuploidy rate and pregnancy outcomes following single thawed euploid embryo transfers (STEET). RESULTS: Sixteen patients with delayed ICSI were included in the study. Twelve were due to poor fertilization and four secondary to immature oocytes. A total of 219 oocytes were retrieved; ten were frozen upon patient request, 168 had standard insemination, and 13 had routine ICSI on the day of retrieval. A total of 129 oocytes underwent delayed ICSI. Sixty-three (49 %) fertilized, 19 (14.7 %) reached blastocysts for biopsy; fivw of which were chromosomally normal (26.3 %). Three patients underwent STEET of a delayed ICSI embryo; all three resulted in live births, including one embryo biopsied on day 8 of development. CONCLUSION: Fertilization failure or an excessive proportion of immature oocytes in an IVF cycle, necessitating delayed ICSI, showed equivalent fertilization and blast formation rates. With the implementation of trophectoderm biopsy and PGS, these embryos can lead to healthy live born babies.

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