Clinical Implementation of Expanded Carrier Screening in Pregnant Women at Early Gestational Weeks: A Chinese Cohort Study

Demands for expanded carrier screening (ECS) are growing and ECS is becoming an important part of obstetrics practice and reproductive planning. The aim of this study is to evaluate the feasibility of a small-size ECS panel in clinical implementation and investigate Chinese couples’ attitudes towards ECS. An ECS panel containing 11 recessive conditions was offered to Chinese pregnant women below 16 gestational weeks. Sequential testing of their partners was recommended for women with a positive carrier status. The reproductive decision and pregnancy outcome were surveyed for at-risk couples. A total of 1321 women performed ECS successfully and the overall carrier rate was 19.23%. The estimated at-risk couple rate was 0.83%. Sequential testing was performed in less than half of male partners. Eight at-risk couples were identified and four of them performed prenatal diagnosis. Our study demonstrated that a small-size ECS panel could yield comparable clinical value to a larger-size panel when the carrier rate of the individual condition is equal or greater than 1%. In addition, more than half of male partners whose wives were carriers declined any types of sequential testing possibly due to a lack of awareness and knowledge of genetic disorders. Genetic education is warranted for the better implementation of ECS.

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A Data-Driven Evaluation of the Size and Content of Expanded Carrier Screening Panels

10.1101/430546 ◽

2018 ◽

Cited By ~ 1

Author(s):

Rotem Ben-Shachar ◽

Svenson MS Ashley ◽

James D. Goldberg ◽

Dale Muzzey

Keyword(s):

At Risk ◽

Detection Rate ◽

Carrier Screening ◽

Data Driven ◽

Carrier Rate ◽

Expanded Carrier Screening ◽

Clinical Detection ◽

The Impact ◽

Variable Impact ◽

Panel Design

ABSTRACTPurposeThe American College of Obstetricians and Gynecologists (ACOG) proposed seven criteria for expanded carrier screening (ECS) panel design. To ensure that screening for a condition is sufficiently sensitive to identify carriers and reduce residual risk of non-carriers, one criterion requires a per-condition carrier rate greater than 1-in-100. However, it is unestablished whether this threshold corresponds with a loss in clinical detection. The impact of the proposed panel-design criteria on at-risk couple detection warrants data-driven evaluation.MethodsCarrier rates and at-risk couple rates were calculated in 56,281 patients who underwent a 176-condition ECS and evaluated for panels satisfying various criteria. Condition-specific clinical detection rate was estimated via simulation.ResultsDifferent interpretations of the 1-in-100 criterion have variable impact: a compliant panel would include between 3 and 38 conditions, identify 11%-81% fewer at-risk couples, and detect 36%-79% fewer carriers than a 176-condition panel. If the carrier-rate threshold must be exceeded in all ethnicities, ECS panels would lack prevalent conditions like cystic fibrosis. Simulations suggest that clinical detection rate remains >84% for conditions with carrier rates as low as 1-in-1000.ConclusionsThe 1-in-100 criterion limits at-risk couple detection and should be reconsidered.

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Clinical Utility of Expanded Carrier Screening: Reproductive Behaviors of At-Risk Couples

10.1101/069393 ◽

2016 ◽

Cited By ~ 3

Author(s):

Caroline Ghiossi ◽

James D. Goldberg ◽

Imran S. Haque ◽

Gabriel A. Lazarin ◽

Kenny K. Wong

Keyword(s):

Decision Making ◽

At Risk ◽

Clinical Utility ◽

Carrier Screening ◽

Reproductive Behaviors ◽

Reproductive Risk ◽

Expanded Carrier Screening ◽

Reproductive Decision Making ◽

Recessive Genes ◽

Professional Guidelines

ABSTRACTPurposeExpanded carrier screening (ECS) analyzes dozens or hundreds of recessive genes for determining reproductive risk. Data on clinical utility of screening conditions beyond professional guidelines is scarce.MethodsIndividuals underwent ECS for up to 110 genes. 537 at-risk couples (ARC), those in which both partners carry the same recessive disease, were invited to a retrospective IRB-approved survey of their reproductive decision making after receiving ECS results.Results64 eligible ARC completed the survey. Of 45 respondents screened preconceptionally, 62% (n=28) planned IVF with PGD or prenatal diagnosis (PNDx) in future pregnancies. 29% (n=13) were not planning to alter reproductive decisions. The remaining 9% (n=4) of responses were unclear.Of 19 pregnant respondents, 42% (n=8) elected PNDx, 11% (n=2) planned amniocentesis but miscarried, and 47% (n=9) considered the condition insufficiently severe to warrant invasive testing. Of the 8 pregnancies that underwent PNDx, 5 were unaffected and 3 were affected. 2 of 3 affected pregnancies were terminated.Disease severity was found to have significant association (p=0.000145) with changes in decision making, whereas guideline status of diseases, controlled for severity, was not (p=0.284).ConclusionMost ARC altered reproductive planning, demonstrating the clinical utility of ECS. Severity of conditions factored into decision making.

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Estimating yields of prenatal carrier screening and implications for design of expanded carrier screening panels

10.1101/429050 ◽

2018 ◽

Author(s):

Michael H. Guo ◽

Anthony R. Gregg

Keyword(s):

At Risk ◽

Exome Sequencing ◽

East Asian ◽

Carrier Screening ◽

Carrier Rate ◽

Ashkenazi Jewish ◽

Careful Selection ◽

Recessive Condition ◽

Selection Of ◽

Genetic Carrier Screening

AbstractPurposePrenatal genetic carrier screening can identify parents at risk of having a child affected by a recessive condition. However, the conditions/genes most appropriate for screening remain a matter of debate. Estimates of carrier rates across genes are needed to guide construction of carrier screening panels.MethodsWe leveraged an exome sequencing database (n=123,136) to estimate carrier rates across 6 major ancestries for 416 genes associated with severe recessive conditions.Results36.5% (East Asian) to 65% (Ashkenazi Jewish) of individuals are variant carriers in at least one of the 416 genes. For couples, screening all 416 genes would identify 0.4-2.8% of couples as being at-risk for having a child affected by one of these conditions. Screening just the 47 genes with carrier rate > 1.0% would identify more than 85% of these at-risk couples. An ancestry-specific panel designed to capture genes with carrier rates > 1.0% would include 6 to 30 genes, while a comparable pan-ethnic panel would include 47 genes.ConclusionOur work guides the design of carrier screening panels and provides data to assist in counseling prospective parents. Our results highlight a high cumulative carrier rate across genes, underscoring the need for careful selection of genes for screening.

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Clinical utility of expanded carrier screening: reproductive behaviors of at-risk couples

Fertility and Sterility ◽

10.1016/j.fertnstert.2016.07.1060 ◽

2016 ◽

Vol 106 (3) ◽

pp. e373

Author(s):

K.K. Wong ◽

K. Ready ◽

C. Lieber ◽

J.D. Goldberg ◽

I.S. Haque ◽

...

Keyword(s):

At Risk ◽

Clinical Utility ◽

Carrier Screening ◽

Reproductive Behaviors ◽

Expanded Carrier Screening

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Clinical Utility of Expanded Carrier Screening: Reproductive Behaviors of At-Risk Couples

Journal of Genetic Counseling ◽

10.1007/s10897-017-0160-1 ◽

2017 ◽

Vol 27 (3) ◽

pp. 616-625 ◽

Cited By ~ 26

Author(s):

Caroline E. Ghiossi ◽

James D. Goldberg ◽

Imran S. Haque ◽

Gabriel A. Lazarin ◽

Kenny K. Wong

Keyword(s):

At Risk ◽

Clinical Utility ◽

Carrier Screening ◽

Reproductive Behaviors ◽

Expanded Carrier Screening

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Expanded carrier screening for preconception reproductive risk assessment: Prevalence of carrier status in a Mexican population

Prenatal Diagnosis ◽

10.1002/pd.5656 ◽

2020 ◽

Vol 40 (5) ◽

pp. 635-643

Author(s):

Carlos Hernandez‐Nieto ◽

Tamar Alkon‐Meadows ◽

Joseph Lee ◽

Teresa Cacchione ◽

Esther Iyune‐Cojab ◽

...

Keyword(s):

Risk Assessment ◽

Carrier Screening ◽

Mexican Population ◽

Carrier Status ◽

Reproductive Risk ◽

Expanded Carrier Screening

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Expanded Carrier Screening in Chinese Population – A Survey on Views and Acceptance of Pregnant and Non-Pregnant Women

Frontiers in Genetics ◽

10.3389/fgene.2020.594091 ◽

2020 ◽

Vol 11 ◽

Author(s):

Hiu Yee Heidi Cheng ◽

Grace Ching Yin Wong ◽

Yuen-Kwong Kelvin Chan ◽

Chin Peng Lee ◽

Mary Hoi Yin Tang ◽

...

Keyword(s):

Pregnant Women ◽

Chinese Population ◽

Carrier Screening ◽

Expanded Carrier Screening

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P–539 The use of expanded carrier screening of gamete donors

Human Reproduction ◽

10.1093/humrep/deab130.538 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

M Payne ◽

A B Skytte ◽

J Harper

Keyword(s):

Web Sites ◽

Muscular Atrophy ◽

Carrier Screening ◽

Carrier Status ◽

National Guidelines ◽

Expanded Carrier Screening ◽

Sperm Donors ◽

International Panel ◽

Registration Number ◽

Alpha Thalassaemia

Abstract Study question What are the sperm and egg donor rejection rates after expanded carrier screening (ECS)? Summary answer Using an ECS panel looking at 46/47 genes, 17.6% of donors were rejected. What is known already The use of ECS is becoming commonplace in assisted reproductive technology, including testing of egg and sperm donors. Most national guidelines recommend rejection of donors if they are carriers of a genetic disease. If the use of ECS increases, there will be a decline in the number of donors available. Study design, size, duration A review of the current preconception ECS panels available to donors was carried out through an online search. The genetic testing results of donors from Cryos International were analysed to determine how many were rejected on the basis of the ECS. Participants/materials, setting, methods Data on gamete donors and their carrier status was provided by Cryos International, who screen donors using their own bespoke ECS panel. The ECS panels identified through the review were compared to the Cryos International panel and data. Main results and the role of chance A total of 16 companies and 42 associated ECS panels were reviewed. There were a total of 2673 unique disorders covered by the panels examined, with a mean of 329 disorders screened. None of these disorders were common to all panels. Cryos International screen 46 disorders in males and 47 in females. From 883 candidate donors, 17.6% (155/883) were rejected based on their ECS result. Carriers of alpha-thalassaemia represented the largest proportion of those rejected (19.4%, 30/155), then spinal muscular atrophy (15.5%, 24/155) and cystic fibrosis (14.8%, 23/155). Limitations, reasons for caution Panel information was found on company web sites and may not have been accurate. Wider implications of the findings: This study highlights the need for consistent EU regulations and guidelines which allow genetic matching of gamete donors to recipients, preventing the need to reject donors who are known carriers. A larger ECS panel would be most beneficial, however, this would not be viable without matching of donors and recipients. Trial registration number Not applicable

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