In vitro fertilization (IVF) has promised hope to many couples struggling with the pain of infertility. However, as with any new medical technology, the ethical implications of this procedure must be examined, particularly in light of recent events such as the birth of the first genetically modified human beings, made possible by IVF. It is crucial to examine oppositions to IVF based on principle, as well as address concerns related to adjacent issues such as the discard of unused embryos; the selection, payment, privacy, and parental rights of donors and surrogates; the importance of genetic parenthood; new combinations of gametes; preimplantation genetic diagnosis and selective implantation; and economic incentives. Short-term justifications shape long-term values, and so we must carefully consider the implications of IVF, even as we maintain compassion and grace toward couples dealing with the difficult realities of infertility.

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PurposeThough copy number variants (CNVs) have been suggested to play a significant role in inborn errors of immunity (IEI), the precise nature of this role remains largely unexplored. We sought to determine the diagnostic contribution of CNVs using genome-wide chromosomal microarray analysis (CMA) in children with IEI.MethodsWe performed exome sequencing (ES) and CMA for 332 unrelated pediatric probands referred for evaluation of IEI. The analysis included primary, secondary, and incidental findings.ResultsOf the 332 probands, 134 (40.4%) received molecular diagnoses. Of these, 116/134 (86.6%) were diagnosed by ES alone. An additional 15/134 (11.2%) were diagnosed by CMA alone, including two likely de novo changes. Three (2.2%) participants had diagnostic molecular findings from both ES and CMA, including two compound heterozygotes and one participant with two distinct diagnoses. Half of the participants with CMA contribution to diagnosis had CNVs in at least one non-immune gene, highlighting the clinical complexity of these cases. Overall, CMA contributed to 18/134 diagnoses (13.4%), increasing the overall diagnostic yield by 15.5% beyond ES alone.ConclusionPairing ES and CMA can provide a comprehensive evaluation to clarify the complex factors that contribute to both immune and non-immune phenotypes. Such a combined approach to genetic testing helps untangle complex phenotypes, not only by clarifying the differential diagnosis, but in some cases by identifying multiple diagnoses contributing to the overall clinical presentation.