Preimplantation Genetic Diagnosis in the Era of Genomic Medicine

Genetic Disease Prevention Begins With Clinician Awareness

Emily L. Mounts, MS


October 27, 2017

Genetic technologies are rapidly reshaping medical practice. In 2016, more than 48,000 genetic tests were ordered, many with the primary goal of confirming a clinical diagnosis and guiding medical decision-making.[1] The explosion of genomic diagnostics is allowing more patients to recognize when their own medical conditions are hereditary and, of importance, to understand the risk for their offspring to be similarly affected. Yet one of the most powerful tools of genetic disease prevention—preimplantation genetic diagnosis (PGD)—is frequently overlooked by clinicians.

What Is PGD, and Who Opts for It?

PGD is a process that allows potential parents to avoid passing on certain genetic disorders to their offspring. PGD can be performed for hundreds of conditions for which there is an identified, serious, disease-causing mutation.

It is often in the preconception or prenatal stage that a couple learns they are at risk of having a child with a genetic condition. This is the stage when genetic carrier screening panels are commonly used to screen for hundreds of rare recessive disorders at once.[2] Couples who opt for these screenings may be unaware beforehand that they both carry a recessive gene mutation associated with a 25% risk for an affected child. Other times, couples seeking PGD may already have a child with a condition such as spinal muscular atrophy or cystic fibrosis.

Increasingly, affected individuals are opting for PGD. These are patients who, in their 20s-40s, developed an autosomal dominant condition, such as hereditary breast or ovarian cancer, cardiomyopathy, Huntington disease, or polycystic kidney disease—or they are at high risk of developing one of these conditions, on the basis of predictive DNA testing. Because these patients have a 50% chance of having a child who could experience the same medical challenges that they, and sometimes their family members, have endured, they are increasingly choosing to invest in measures to avoid transmission of their disease to the next generation.[3]

How Does PGD Work?

In experienced hands, PGD is usually straightforward and low-risk. Embryos are created through in vitro fertilization (IVF), grown in the laboratory for 5-6 days, and laser-biopsied to obtain a handful of cells from the embryo's future placenta. While the embryos are frozen, the biopsied cells undergo genetic testing that is customized to accurately detect the family's particular mutations. Embryos without the familial disease gene are identified and transferred into the uterus, avoiding occurrence of the genetic condition in the offspring.

Current expert consensus is that PGD poses few risks to the embryo, the resulting fetus/baby, or the mother. Although rare misdiagnoses have been reported and patients should be counseled about the residual risk they face with any test result,[2] the overall accuracy of PGD is high and the vast majority of patients will have children who are free of the tested condition.

Growing Capacity for PGD to Help Create Healthy Families

From the inception of PGD in 1989 until recently, the most common indications were rare genetic disorders with high morbidity and mortality, such as cystic fibrosis, sickle cell anemia, and Tay-Sachs disease.[3] But the dramatic shift into genomic medicine is creating a new, broader segment of PGD candidates that is supported by recent improvements in embryo biopsy and vitrification, IVF success rates, and PGD accuracy.[3] This shift is primarily being facilitated by next-generation genetic sequencing technology, which, owing to its lower costs, rapid turnaround times, and ability to multiplex samples from several patients at once, is providing greater access to DNA diagnostics. With the number of patients receiving mutation-based diagnoses growing by the day, the fields of obstetrics, oncology, cardiology, and neurology in particular are seeing more patients with documented genetic etiologies for their disorders.[4,5]

When patients such as these are at or are reaching reproductive age, they should be made aware of the option of PGD. They often shoulder a large emotional burden as they cope not only with their own medical challenges but also with the fear that they could transmit their disorders to their children.[4] Some couples remain childless because of this fear or the anxiety of invasive prenatal diagnosis, after which the only fully preventive option is pregnancy termination.[5,6]

PGD, however, has been shown to "rekindle optimism" and provide a sense of control and hope, and is psychologically and ethically preferred by future parents.[4,7] Moreover, cost/benefit analysis demonstrates that IVF with PGD may be the most economical way for couples at risk of transmitting certain genetic disorders to build their families.[8]

Importance of Raising Awareness of PGD

Despite being one of the most effective tools for genetic disease prevention, PGD is rarely brought to light.

Potential PGD candidates are frequently unaware of or confused by it. When they do learn of PGD, they may fear damaging the embryo or express concerns about test reliability, the IVF procedure, or success rates.[6] Although most of these concerns could be largely alleviated by healthcare providers, physicians cite having insufficient knowledge to educate patients,[9] and in many cases do not feel comfortable offering, interpreting, or counseling on genetic testing.[10,11,12]

This is problematic, considering that some patients express a preference to discuss PGD with a physician with whom they have an ongoing relationship, such as their oncologist or obstetrician.[13] For this reason, professional education to facilitate a wider understanding of PGD and determine how to best incorporate PGD into clinical discussions is essential. There may even be liabilities associated with physicians' failure to inform patients of the option.[4] Until the medical community is more educated on the benefits of PGD, countless patients will create their families unaware of the option to avert disease risks in their offspring.

Many factors will ultimately influence a potential PGD candidate's reproductive plan: the specific disease course, treatment options, and life expectancy; their religious background; insurance coverage and finances; and acceptability of the alternatives.[6] But as genomic advances continue to reform medical practice, it is worth a broad professional effort to facilitate a better understanding of, and accessibility to, PGD. There is little doubt these efforts will be well received by patients, whose optimism and hope can be restored by this powerful path to parenthood.


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