Expanded preconception carrier screening for infertile couples

Expanded preconception carrier screening for infertile couples


The importance of genetic screening in IVF treatments in order to avoid reproductive disorders.

In developed countries single-gene diseases collectively account for 20% of infant mortality and approximately 10% of pediatric hospitalizations (1-2). The ultimate aim of preconception carrier screening (PCS) panels is to increase the reproductive autonomy of the individuals and couples by providing preconception knowledge that could inform them of the available treatment options. The options after PCS in general, and expanded PCS in particular, include preimplantation genetic testing for monogeneic disease (PGT-M), the use of gamete donors, conceiving without further testing after thorough genetic counseling, adoption, and refraining from having children (3).

In patients who undergo PCS, it is important that they are aware of the fact that it cannot be guaranteed that PGT-M will be available for their genetic condition, although this occurs rarely. Further, it must also be taken into account that family history may be lacking in carriers, de novo mutations and germline mosaicism can occur, and conditions may have variable penetrance and expressivity. However, the PCS informs both their reproductive decision making as well that of their offspring.

With comprehensive panels where healthy individuals are likely to be identified as carriers for several conditions, testing of carrier status for embryos and prioritization of the embryos to transfer needs to be considered. According to ESHRE, ‘there is no good reason for rejecting PGT in order to avoid health problems in a third generation’ (4). Although this was related to X-linked mutation and sex selection, it is reasonable to assume the same principle should apply to rare autosomal recessive conditions. Given the parental desire to provide children with the easiest possible route in life, patients may feel that this would be appealing to avoid any reproductive barriers in a third generation (5).

Further, it is not an uncommon practice in PGT-M to select against mutations for conditions with reduced penetrance to lessen the burden of medical disease on the family (6). In agreement with this, ESHRE has stated that consideration on an individual basis should be given to PGT-M for disorders with incomplete penetrance in view of, among other factors, ‘the seriousness of the disease in the particular [family] (…) and personal experiences and circumstances of the individual applicants’ (4).

The cost of caring for children with inherited conditions has risen drastically. The causes of the increased cost can be attributed to novel pharmacological products, approach to prophylactic and targeted treatments, and advancements in healthcare that result in a longer life expectancy. In contrast, genetic testing is getting cheaper. Expanded PCS utilizing next generation sequencing has greatly reduced the per base cost relative to Sanger sequencing, enabling lower-cost sequencing at a faster rate. Coupled with improved bioinformatic data analysis, this sequencing technology has enabled widespread use. The individual and societal costs associated with caring for affected individuals outweigh the costs of expanded PCS and PGT-M for these families.

Post by Dr. Jason Franasiak – Chief Medical Officer of IVIRMA America /RMA New Jersey


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2. Kumar, P., Radhakrishnan, J., Chowdhary, M.A., Giampietro, P.F. Prevalence and patterns of presentation of genetic disorders in a pediatric emergency department. Mayo Clin Proc. 2001;76:777–783.

3. Carolina Vaz-de-Macedo, Joyce Harper; A closer look at expanded carrier screening from a PGT perspective, Human Reproduction, Volume 32, Issue 10, 1 October 2017, Pages 1951–1956.

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5. Carolina Vaz-de-Macedo, Joyce Harper; A closer look at expanded carrier screening from a PGT perspective, Human Reproduction, Volume 32, Issue 10, 1 October 2017, Pages 1951–1956.

6. Franasiak JM, Olcha M, Bergh PA, Hong KH, Werner MD, Forman EJ, Zimmerman RS, Scott RT Jr. Expanded carrier screening in an infertile population: how often is clinical decision making affected? Genet Med. 2016 Nov;18(11):1097-1101.

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10. Martin J1, Asan2, Yi Y2, Alberola T3, Rodríguez-Iglesias B3, Jiménez-Almazán J3, Li Q4, Du H2, Alama P5, Ruiz A5, Bosch E5, Garrido N4, Simon C6. Comprehensive carrier genetic test using next-generation deoxyribonucleic acid sequencing in infertile couples wishing to conceive through assisted reproductive technology. Fertil Steril. 2015 Nov;104(5):1286-93.

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12. Frati PGulino MTurillazzi EZaami SFineschi V. The physician’s breach of the duty to inform the parent of deformities and abnormalities in the foetus: “wrongful life” actions, a new frontier of medical responsibility. J Matern Fetal Neonatal Med. 2014 Jul;27(11):1113-7.

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