Clinical utility of reproductive carrier screening for preconception and pregnant couples for multiple genetic conditions: a systematic review and meta-analysis

ABSTRACT

Introduction

Many scientific societies have emphasized the importance of evaluating the clinical utility of reproductive carrier screening (RCS). This systematic review aims to assess the clinical utility of RCS and synthesize the outcomes in a meta-analysis.

Areas covered

A total of eleven studies were included. The number of conditions screened in the studies varied from three to 176 and led to the identification of one to 24 high-risk couples (HRCs) per 1,000 screened individuals. Pooled estimations were as follows: the prenatal diagnosis (PND) rate among pregnant HRCs 0.644 (95% CI = 0.364, 0.923), the termination rate among affected pregnancies 0.714 (95% CI = 0.524, 0.904), and the rate of in-vitro fertilization (IVF) with preimplantation genetic testing (PGT) 0.631 (95% CI = 0.538, 0.725). There is a statistically significant decrease in the rates of undertaking PND and termination as the number of screened conditions increases. Carriers of conditions classified as having a more severe impact were found to be more likely to choose termination or IVF with PGT.

Expert Opinion

Our review suggests that the number and the severity of screened conditions can significantly impact HRCs’ reproductive decisions. Future work needs to investigate the definition of clinical utility and the design of screening panels.

KEYWORDS:

• Systematic review
• meta-analysis
• clinical utility
• reproductive carrier screening
• expanded carrier screening
• autosomal recessive
• X-linked

Acknowledgement

The Australian Reproductive Genetic Carrier Screening Project (Mackenzie’s Mission) is funded by the Australian Government’s Medical Research Future Fund as part of the Genomics Health Futures Mission (GHFM), grant GHFM73390 (MRFF-G-MM). The grant is administered by the Murdoch Children’s Research Institute through Australian Genomics.

Article highlights

• Many scientific societies have recommended that reproductive carrier screening (RCS) should be implemented for prospective couples and ideally prior to pregnancy. More importantly, they emphasize that assessing clinical utility of RCS is critical when considering the effectiveness of carrier screening programs.

• Our review found that many high-risk couples took reproductive actions to avoid having a child with a genetic condition identified by reproductive carrier screening through either pregnancy termination for pregnant couples or in-vitro fertilization with preimplantation genetic testing for preconception couples.

• Our review also found that high-risk couples were more likely to take reproductive actions when they were found to be at risk of having children with more severe conditions.

• According to the meta-regression analyses in our review, a decrease of the rates of undertaking prenatal diagnosis and termination can be found when the number of screened conditions increases.

• Genetic counseling is valued by couples to fully understand the screened conditions, risk, and reproductive options.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14737159.2023.2206519.

Additional information

Funding

Paul Scuffham is the recipient of a NHMRC Senior Research Fellowship – SRFB (#1136923); Martin Downes is partly funded by the Mackenzie's Mission project, which is under the Genomics Health Futures Mission, part of the Australian Government's Medical Research Future Fund.