How to Manage Expectations in Embryo Diagnostics in IVF?

PATIENT EXPECTATIONS

As infertility is defined as 6–12 months without conception, by the time patients seek care, their patience is already tested. Since the birth of Louise Brown in 1978, the field has been transformed and now enjoys success more than failure. This has naturally changed the expectations of both providers and patients when it comes to outcomes. Further, what defines success has changed over the decades, with a focus now being on a healthy singleton delivery. The advent of embryo diagnostics, with a promise of insights into the genetic health and viability of embryos, often amplifies these expectations. It is not merely about achieving successful conception any longer—it is about a healthy child in a short period of time. Couples who repeatedly fail to conceive before and after ART will inevitably look for possible explanations and become vulnerable to accepting and/or seeking interventions proposed to increase their chances of conception. Possible options are often presented by word of mouth, the Internet, and other means. One domain that rallies the very core of those vulnerabilities is the possibility of conducting embryo diagnostics. Indeed, the ability to extend embryo culture to the blastocyst stage and vast improvements in embryo cryopreservation offers new embryo diagnostic options. These options are accompanied by new hopes and new challenges.

PATIENT AUTONOMY

Empathetic communication with patients plays a vital role in managing the ‘‘EVERYTHING’’ expectation. Clinicians should understand and validate patient concerns providing a supportive space for them to express their queries. At the same time, concerted efforts should be made to avoid performing every diagnostic test for every patient. The decision to apply a diagnostic test needs to be made in the context of the individual patient, their diagnosis, and their prognosis, even when a patient states they want ‘‘EVERYTHING’’ done.

Balancing patient autonomy with clinician counseling is a fundamental principle in ethical medical practice. With embryo diagnostics, this principle entails ensuring that patients' decisions are informed by a comprehensive understanding of the risks and benefits involved. Ensuring that clinicians have a clear understanding of the development and analytical evaluation of a test, establishment of its predictive values, and assessment of its efficacy, in both your own laboratory and the published literature, is imperative to accomplish this task.

ROLE OF THE PROVIDER AS EDUCATOR

It is important to inform patients that <100% successful outcomes of ART stem from the inherent limitations of human reproduction. Although ART may outperform natural conception (courtesy of multiple ovulation and various methods of embryo selection), it remains limited by the inherently poor efficacy of human reproduction. This includes treatments that employ embryo diagnostics. It is important for providers to understand the benefits and the risks of current embryo diagnostic technologies. Clinicians will inevitably find themselves in the position of aligning patient hopes with the scientific boundaries of the medical interventions. This task is particularly challenging in the context of embryo selection techniques, such as preimplantation genetic testing (PGT) for aneuploidy (PGT-A), polygenic embryo screening, time-lapse imaging, and other advanced procedures. The nature of the tests themselves and the specific aspect of embryo health that they evaluate differ widely, and each class of diagnostics, or prognostics, may have unique, specific goals.

EMBRYO DIAGNOSTICS: BENEFITS

Assessing embryo development offers many possibilities for decision making. Analyzing embryonic genetic material can be used to screen for or diagnose heritable or de novo abnormality that may confer morbidity or mortality to the child. Conversely, genetic material can be used as a prognostic feature for the ability of an embryo to implant and achieve a live birth. In this case, prognosis is not about predicting the course of disease but instead the chances of achieving a live birth with the use of ART. The use of genetic material for multiple, often overlapping goals is complex and can be misunderstood by both the clinician and the parents.

Genetic testing of embryos can be classified as PGT-A, which screens for whole chromosome aneuploidy, segmental chromosome aneuploidy, and mosaicism, depending on the testing platform; PGT for monogenic diseases, which screens for single gene mutations; PGT for structural rearrangements, which screens for chromosome translocations; and polygenic embryo screening, which estimates the likelihood of developing future conditions or traits in the child that is conceived.

There are various goals for these diagnostic approaches. For PGT for monogenic diseases, the goal is to diagnose a single gene mutation. This embryo diagnostic is most intuitive. For PGT-A, the goal is to reduce the chance of transferring trisomies that are viable or those that result in first trimester pregnancy loss by selecting embryos that have been diagnosed with lacking these chromosomal abnormalities. Aneuploidy is the most common reason for failure of implantation or miscarriage, and selecting what is thought to be a euploid embryo would, in theory, result in a higher chance of implantation and live birth. Further, aneuploid embryos that are detected and not transferred may reduce the chance of miscarriage and, thus, may reduce the time to pregnancy and failed embryo transfers. It is important to discuss with the patient that the use of genetic testing of embryos simply ranks embryos with those thought to lack a single gene disorder or chromosomal aneuploidy being ranked higher than those thought to have the disorder or aneuploidy—genetic testing itself does not change the embryo itself or guarantee a healthy pregnancy.

EMBRYO DIAGNOSTICS: LIMITS/HARMS

Although these technologies offer the potential for embryo selection, they also come with their own set of limitations and ethical considerations. It is crucial for practitioners to effectively communicate these limitations to patients. An overreliance on, or misapplication of, these technologies can lead to unnecessary emotional distress and complex ethical dilemmas, especially when it comes to decisions about discarding embryos on the basis of embryonic diagnostic results. The clinical advantage of these tests is attained by correctly identifying those embryos with little or no reproductive potential and ranking embryos accordingly. However, patients should be warned that other factors unrelated to ploidy status impact and limit sustained implantation rates including impaired endometrial receptivity, aberrant embryonic-endometrial synchrony, and inadequate luteal support. Further, it should be noted that assessment of embryos with genetic testing or otherwise is not therapeutic. It is a diagnostic used to identify those embryos within an individual cohort which are more likely to lead to a live birth. It is important to note that nothing done in medicine has zero risk and the concept of residual risk must be explained. The tests that are used, even those that have been validated and proven to be effective, do not guarantee a healthy pregnancy. It should be discussed that screened embryos may not result in a pregnancy at all, may result in a miscarriage, or may result in a child with the disorder that was screened due to intrinsic fallibility of the test ordered. Further, it is important to note that embryo diagnostics such as PGT are not a single test. Each platform and testing methodology must be evaluated individually. Each individual test may vary in its ability to diagnose euploidy, mosaicism, and subsequent live birth rates

PATIENT COUNSELING

To discuss diagnostic tests, the clinician should have information about the safety, efficacy, predictive value, and the cost of the technique. Familiarity with the development, validation, and ongoing quality assurance/quality control requires an up-to-date knowledge of the medical literature. As with clinical diagnostics, new randomized controlled trials may shed light of the performance of the diagnostic test showing that it may not be effective in certain patient populations, such as PGT in oocyte donor–derived embryos or may, potentially, be detrimental. These data must be reviewed and distilled for patients to effectively counsel them. To effectively have these conversations with patients, it is imperative to understand the four phases of embryo diagnostics validation: analytic validation; predictive value studies; randomized control trials; and ongoing quality assurance/ quality control and surveillance. The first three are imperative to understanding the effectiveness of an embryo diagnostic intervention. Many embryo diagnostics do not have all three of these phases completed before being made commercially available. Further, various studies can have conflicting results. This has been seen with PGT-A, with some randomized control trials showing benefit, whereas others fail to do so. Understanding the potential reasons behind this variation is important.

Managing patient expectations in the context of embryo diagnostics in in vitro fertilization represents a complex and sensitive task, which demands empathy, ethical mindfulness, and an understanding of the evolving technologies. By effectively communicating the benefits and limitations, clinicians can assist patients in navigating their infertility journey with realistic expectations and informed consent. This balanced approach is crucial in providing evidence based, patient-centered care in the field of reproductive medicine. When a patient presents stating ‘‘I want a healthy infant and I want everything done,’’ it is imperative to ensure that a careful discussion is performed regarding the embryo diagnostics available, noting that a ‘‘healthy infant’’ is not possible to guarantee and that having ‘‘everything done’’ does not include ordering every unvalidated test that exists.

Source: Jason Franasiak, Paul Pirtea; Fertil SterilVOL. 124 NO. 5P1 / NOVEMBER 2025

https://doi.org/10.1016/j.fertnstert.2025.05.161