We found low rates of prenatal diagnostic testing within our PGT-M cohort, with less than one in ten individuals undergoing confirmatory prenatal diagnosis. This was despite all patients routinely receiving genetic counselling on the limitations of PGT-M and recommendations for follow-up prenatal diagnosis.

While our rate of uptake is similar to reported rates for confirmatory testing after PGT-A, it is lower than previous reports of PGT-M cohorts [7]. Differences in uptake may be due to variations in PGT-M and prenatal care practice across clinics, including counselling surrounding PGT-M and its limitations, and differences in PGT-M protocols such as concurrent aneuploidy screening and test accuracy, and differences in accessibility including cost of treatment. In the 2022 study by Bunnell et al., 44% of patients did not have aneuploidy screening performed on their embryos prior to transfer [10]. In contrast, all embryos in our cohort were concurrently screened for aneuploidy. It is possible our cohort were therefore less likely to have another indication for testing, such as a high probability aneuploidy screening result, or due to ultrasound anomaly. In contrast, Toft et al.’s 2022 study found that most respondents who undertook CVS following PGT-M cited clinical recommendations as a motivating factor. This may indicate this cohort received different counselling on the limitations of PGT-M compared to our cohort, possibly influencing their decision to pursue confirmatory testing.

Although the current study did not collect data on patient decision making, previous research suggests reasons for declining confirmatory prenatal testing include concern regarding procedure-related miscarriage, feeling as though testing outcomes would not alter pregnancy decision-making, and misunderstanding of testing recommendations [11, 26, 27]. Additionally, patients may weigh the residual risk of misdiagnosis against the risk of confirmatory testing.

Low uptake may reflect low patient acceptance of existing guidelines. While existing guidelines were primarily developed to facilitate informed consent, the recommendation for prenatal diagnosis may also be perceived by patients as a defensive practice to protect providers from litigation. It is crucial that clinical guidelines are patient-centred, rather than developed due to medico-legal concerns [28]. Incorporating patient preferences into the development of clinical guidelines facilitates shared decision-making, enables informed consent, and builds patient engagement [29, 30]. This approach supports effective healthcare delivery and promotes patient autonomy, aligning with ethical practice.

Three trends were noted during our analysis. Among those that undertook prenatal diagnostic testing, there was (i) a greater proportion of conditions with profound severity; (ii) there were a smaller proportion of conditions that were adult onset; and (iii) a smaller proportion of conditions amenable to treatment. While these trends were not statistically significant, due to the small size of each subgroup, each trend is clinically plausible and is consistent with our clinical experiences of patient decision-making.

These trends may be explained by various factors which influence an individual’s decision to undertake prenatal diagnostic testing. Individuals may confirm the genetic status of their pregnancy to gain reassurance, prepare for the birth of a child with a genetic condition, or to inform pregnancy outcomes, such as termination of pregnancy. When considering pregnancy outcomes, patients often reflect on the quality of life of a child with the genetic indication [31].

A 2013 study exploring reasons for termination in the setting of fetal anomalies reported that for many pregnant people, the emotional trauma of delivery a baby with poor quality of life dictated their decision-making [12]. It is possible that individuals feel inclined to confirm conditions of profound severity, as this information is more likely to inform pregnancy outcomes. Perceived severity is a key dimension in the Health Belief model, a framework used to explain health behaviour acceptance [32]. Within this model, patients are more likely to undertake a health behaviour to avoid conditions they perceive to be severe [33]. Extending from this, it is possible patients feel a greater need to confirm the accuracy of PGT-M in the context of conditions with greater severity.

Consideration of quality of life may also contribute to the lower testing uptake observed for conditions that are adult onset or have preventative treatment options available. While adult-onset conditions can greatly affect the quality of life in later years, there is the possibility of good quality of life preceding condition onset [34]. This may make individuals feel more comfortable utilising PGT-M as a risk reduction approach alone, and patients may feel less concerned with receiving diagnostic confirmation of the prenatal genetic status [35]. Additionally, individuals may feel more comfortable utilising PGT-M to reduce reproductive risk for conditions where preventative treatment options are available, as these can drastically improve prognostic outcomes and subsequent quality of life of affected individuals [36]. The observed low testing uptake for adult-onset conditions and those with preventative treatment options may reflect these perceptions.

Prenatal diagnosis for adult-onset conditions can raise unique ethical concerns. As highlighted earlier, termination of pregnancy may not feel appropriate due to perceived quality of life prior to condition onset. However, if testing is conducted without the intention to terminate in the context of a positive result, it may disregard the autonomy of the future individual (the ‘right not to know’ one’s genetic status) [34]. Individuals may also be hopeful that future treatment options could alter the prognosis of adult-onset conditions [36, 37]. These ethical considerations and optimism for future treatment options may also contribute to the lower testing uptake observed for adult-onset conditions.

The current study is limited by the small size of the prenatal diagnosis group, which limited the statistical significance of our subgroup analysis. This analysis is therefore exploratory, identifying potential trends to guide future research directions. Further investigation through larger quantitative studies and qualitative research will be valuable to explore possible associations between condition characteristics and confirmatory testing uptake. Our study is also limited by being a single-centre study. While our fertility centre is one of the state’s largest PGT-M providers, there may be variation in uptake rate across different fertility centres that is missed by the current study. Additionally, we were not able to measure the PGT-M misdiagnosis rate in our cohort due to the unavailability of data on postnatal outcomes. However, as the primary aim was to analyse patient uptake of prenatal diagnosis rather than evaluate the accuracy of PGT-M, this limitation did not affect our ability to answer the research question. Finally, as we did not collect information on patient decision-making, we are only able to speculate on reasons for the observed low uptake.

This study contributes important data to an underresearched area. The study’s strengths include the consistent use of karyomapping over the study period and the consistent provision of genetic counselling, including discussion surrounding the limitations of testing, to all patients. This reflects current laboratory practice and enables concurrent aneuploidy screening on all embryos transferred during the study period. This reduces the chance of prenatal diagnosis undertaken due to aneuploidy confounding results. Our study is also strengthened by using a state-wide dataset for linkage.

Our results demonstrate low prenatal diagnosis uptake in our PGT-M population. Further research using patient-reported outcomes are needed to understand why most individuals do not follow recommendations to have prenatal diagnostic testing in a PGT-M conception. Qualitative research exploring the decision-making process is needed to understand patient perceptions, preferences, and experience, and could be used to improve genetic counselling of this indication group. Future research should also explore patient acceptance of existing guidelines.