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CF
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Other key considerations
There are a number of factors to consider, from a practical perspective, when requesting RGCS.
Follow-up is critical to ensure that screening of the male partner occurs when the female partner is identified as a carrier for an AR condition.
It can take up to two weeks from sample collection to results being available for three-gene RGCS. This means that when screening is urgent— for example, when a couple is already pregnant— it may be appropriate to test both partners at the same time to expedite a result.
A couple’ s reproductive risk is the same for every pregnancy and independent of maternal age. However, a change in reproductive partner warrants a reassessment of reproductive risk.
Individuals with a family history of a genetic disorder are most appropriately screened using a test that detects the genetic variants or genetic disorder in their family.
RGCS for an expanded set of AR and XL genetic disorders may be a more appropriate option for individuals from a non-European background or for couples with disparate ethnic backgrounds. 13 Early data also supports the use of expanded RGCS in consanguineous couples. 12
It is important to note that some laboratories only offer expanded screening as a combined test for couples, which may not be appropriate for all clinical scenarios.
Occasionally there can be incidental findings for carriers; for example, increased risk of premature ovarian
When screening is urgent, it may be appropriate to test both partners at the same time. failure for FMR1 premutation carriers. 8 Although identifying this is not the purpose of screening, these findings confer important medical information for the carrier.
Understanding funded RGCS
The MBS-funded three-gene RGCS requires testing of the female partner first( MBS item 73451), followed by testing of the male partner only if the female is identified as a carrier for CF or SMA( MBS item 73452).
This approach ensures both partners are screened appropriately for all three disorders covered by three-gene RGCS( males are not offered carrier testing for FXS as they are not unaffected carriers for XL disorders) and avoids unnecessary testing of the male partner( given that 95 % of the time the female partner will not be a carrier). 2
Therefore, to access MBS-funded threegene RGCS for male patients, it is essential to inform the testing laboratory that the female partner is a carrier for CF and / or SMA.
This will also enable the laboratory to provide a more precise reproductive risk estimate for the couple in the report.
A fact sheet explaining the use of items 73451 and 73452 is available from MBS Online( see online resources).
Use of funded items so far
Following significant advocacy from patient, clinical and research groups, and a successful application to the Medical Services Advisory Committee by the Royal College of Pathologists of Australasia,
Figure 1. Services under MBS items for three-gene screening, November 2023 to June 2024, by sex.
three-gene RGCS was introduced on the MBS in November 2023.
Review of the publicly available data so far reveals that the uptake of threegene RGCS was immediate and high( see figure 1), 14 with service volumes halfway through 2024 at 59 % of total volumes anticipated for 2024. So far, the number of males tested as a proportion of females is lower than expected from previous Australian research( 3 % vs 4.6 %, p value < 0.05). 2
This could reflect real-world incomplete uptake by male partners despite the female partner being identified as a carrier for an
15, 16
AR disorder.
Conclusion
RGCS for couples planning pregnancy or in early pregnancy in Australia represents an important step in offering informed reproductive planning for couples at risk. Uptake has steadily increased following the MBS-funding of three-gene screening in November 2023. However, there may be gaps still to fill, by following up male partners of females who have been identified as carriers.
References on request from kate. kelso @ adg. com. au
Online resources
MBS data accessed from Services Australia( online). 14
• MBS fact sheet on three-gene reproductive genetic carrier screening bit. ly / 3Bv7KFG