Comprehensive carrier genetic test using next generation deoxyribonucleic acid sequencing in infertile couples wishing to conceive through assisted reproductive technology

The comprehensive carrier genetic screening test developed here offers a powerful tool to detect alleles for hundreds of Mendelian diseases in patients.


Julio Martin, Ph.D., Asan, Ph.D., Yuting Yi, M.S., Trinidad Alberola, Ph.D., Beatriz Rodríguez-Iglesias, Ph.D., Jorge Jiménez-Almazán, Ph.D., Qin Li, B.S., Huiqian Du, M.S., Pilar Alama, M.D., Amparo Ruiz, M.D., Ernesto Bosch, M.D., Nicolas Garrido, Ph.D., Carlos Simon, M.D.

Volume 104, Issue 5, Pages 1286-1293



To develop an expanded pan-ethnic preconception carrier genetic screening test for use in assisted reproductive technology (ART) patients and donors.


Retrospective analysis of results obtained from 2,570 analyses.


Reproductive genetic laboratory.


The 2,570 samples comprised 1,170 individuals from the gamete donor programs; 1,124 individuals corresponding to the partner of the patient receiving the donated gamete; and 276 individuals from 138 couples seeking ART using their own gametes.



Main Outcome Measure(s):

Next-generation sequencing of 549 recessive and X-linked genes involved in severe childhood phenotypes reinforced with five complementary tests covering high prevalent mutations not detected by next-generation sequencing.


Preclinical validation included 48 DNA samples carrying known mutations for 27 genes, resulting in a sensitivity of 99%. In the clinical dataset, 2,161 samples (84%) tested positive, with an average carrier burden of 2.3 per sample. Five percent of the couples using their own gametes were found to have pathogenic variants conferring high risk for six different diseases. These high-risk couples and patients received genetic counseling and recommendations for preimplantation genetic diagnosis. For patients receiving gamete donation, we applied a genetic testing and blinded matching system to avoid high-risk combinations regardless of their carrier burden. For female donors, 1.94% were positive for X-linked conditions; they received genetic counselling and were discarded.


We have developed a comprehensive carrier genetic screening test that, combined with our matching system and genetic counseling, constitutes a powerful tool to avoid more than 600 Mendelian diseases in the offspring of patients undergoing ART.

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