Prevalence and Treatment Choices for Couples with Recurrent Pregnancy Loss Due to Structural Chromosomal Anomalies.

OBJECTIVE: Parental carriers of balanced structural chromosomal rearrangements such as reciprocal or Robertsonian translocations are at increased risk of recurrent pregnancy loss (RPL) due to the production of gametes with unbalanced non-viable chromosome variants. As a purported means of improving reproductive outcomes in this population, IVF and preimplantation genetic diagnosis (PGD) have been introduced as an alternative to natural conception and prenatal diagnosis. In this study, we evaluate the prevalence and treatment choices of couples with structural chromosomal rearrangement referred to a tertiary care RPL clinic. In addition, we compare the two methods of management in terms of live birth rate. METHODS: This is a retrospective chart review of 2321 couples who were referred to a highly specialized RPL clinic for ongoing clinical management between January 2005 and December 2013 (n = 23). Couples who pursued PGD through local fertility centres during this time were also included (n = 13). RESULTS: Thirty-six couples (1.6%) were found to be parental carriers of a structural chromosomal rearrangement. In this cohort, couples were twice as likely to pursue natural conception compared with IVF with PGD. No significant differences were observed in live birth rate between PGD and clinical management (66.6% vs. 53.3%, P = 0.717). With PGD management, six live birth outcomes were observed, with an incidence of one birth in 5.63 years of follow-up. With clinical management, 24 live birth outcomes were observed, with an incidence of one birth in 4.09 years of follow-up. Mean time to live birth was 17.5 months and 23.3 months in clinical management and PGD, respectively. CONCLUSIONS: Among couples presenting to a tertiary RPL clinic, parental carriers of structural chromosomal rearrangement and history of RPL are more likely to pursue natural conception over IVF and PGD. With regards to reproductive outcomes, no significant difference in miscarriage rate, time to live birth, or live birth rate was observed between couples who pursued PGD compared with expectant clinical management.

GeneYenta: a phenotype-based rare disease case matching tool based on online dating algorithms for the acceleration of exome interpretation.

Advances in next-generation sequencing (NGS) technologies have helped reveal causal variants for genetic diseases. In order to establish causality, it is often necessary to compare genomes of unrelated individuals with similar disease phenotypes to identify common disrupted genes. When working with cases of rare genetic disorders, finding similar individuals can be extremely difficult. We introduce a web tool, GeneYenta, which facilitates the matchmaking process, allowing clinicians to coordinate detailed comparisons for phenotypically similar cases. Importantly, the system is focused on phenotype annotation, with explicit limitations on highly confidential data that create barriers to participation. The procedure for matching of patient phenotypes, inspired by online dating services, uses an ontology-based semantic case matching algorithm with attribute weighting. We evaluate the capacity of the system using a curated reference data set and 19 clinician entered cases comparing four matching algorithms. We find that the inclusion of clinician weights can augment phenotype matching.