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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Nurs Womens Health. Author manuscript; available in PMC Jul 30, 2012.
Published in final edited form as:
PMCID: PMC3408233
NIHMSID: NIHMS392986
Unraveling Preimplantation Genetic Diagnosis for High-Risk Couples Implications for Nurses at the Front Line of Care
Patricia E. Hershberger, PhD, APRN, FNP-BC, Catherine Schoenfeld, MSN, CNM, WHNP, and Ilan Tur-Kaspa, MD
Patricia E. Hershberger, Assistant professor and NIH BIRCWH Faculty Scholar at the University of Illinois at Chicago College of Nursing and College of Medicine in Chicago, IL;
Address correspondence to: phersh/at/uic.edu
Two decades have passed since preimplantation genetic diagnosis (PGD) was successfully used to benefit high-genetic-risk couples with a known genetic disorder. This novel reproductive option allows couples the ability to find out important genetic information about their embryos prior to establishing a pregnancy. For many couples, the awareness of specific genetic mutations or markers of their in vitro embryos avoids the anguishing decision often associated with traditional prenatal diagnosis—whether or not to terminate an ongoing pregnancy (Chamayou et al., 1998; Palomba et al., 1994).
The case study exemplar presented here (see Box 1) serves as a poignant example of the context and particulars that are representative of a growing number of couples who seek foundational information about PGD, a primary prevention measure, from their front line health care providers. Often these providers are nurses, midwives and nurse practitioners in women’s health. Like Colette and Christopher of the case exemplar, many couples are in search of accurate health information, education and anticipatory guidance surrounding PGD.
Box 1. Case Exemplar
Colette, 32 years of age, and Christopher, 35 years of age, are the parents of a 4-year-old son who is diagnosed with cystic fibrosis, an autosomal recessive genetic disorder, resulting from a mutation at the CFTR gene, delta-F508. Before their son’s birth, Colette and Christopher were unaware of their genetic risk to transmit cystic fibrosis. Then their son was diagnosed with meconium ileus, an intestinal obstruction present at birth, which required immediate surgery to correct. Meconium ileus is the first symptom to appear in approximately 15 percent to 20 percent of children with cystic fibrosis. The other most common symptoms of cystic fibrosis among children include recurrent lung disease, chronic abdominal pain, pancreatic insufficiency and failure to thrive. In this case, confirmatory sweat and genetic testing resulted in a positive diagnosis for cystic fibrosis. At present, the couple desires to have another child but is worried that their future offspring may also have cystic fibrosis. Through an Internet support group, the couple became aware of preimplantation genetic diagnosis, or PGD. Colette and Christopher reside in the United States and are curious about PGD. While undergoing a routine gynecological examination, Colette turns to the nurse, her trusted health care provider, for information and education about PGD.
This article provides updated information on PGD applications as a primary prevention measure, presents a succinct overview of PGD procedures and highlights current advances and implications for nurses, advanced practice nurses, midwives, physicians and other health care providers to optimize patient education surrounding PGD use for high-genetic-risk couples. It’s important to note that there are differences in government regulation and legislation from country to country surrounding PGD; therefore, this article focuses on caring for couples in the United States.
The first application of PGD in humans was described in the United States in 1990 (Verlinsky et al., 1990) and concurrently in the United Kingdom (Handyside, Kontogianni, Hardy, & Winston, 1990). PGD of the embryo was performed for couples at high risk for transmitting an X-linked genetic disorder to their future offspring by identifying and selecting female embryos (Handyside et al.). Since the initial application, couples at high risk for transmitting X-linked disorders have continued to use PGD in growing numbers, and so have other high-genetic-risk couples. Initially, however, PGD use increased slowly. Recent data suggest an increase in use, with more than 600 infants born worldwide in a 1-year period alone (Goossens et al., 2008). The number of genetic disorders for which PGD can be used also continues to climb steadily with estimates at 170 different genetic disorders (Preimplantation Genetic Diagnosis International Society, 2008). Box 1 lists current applications for PGD for high-genetic-risk couples.
The most recognized and widespread application of PGD for high-genetic-risk couples is to prevent single gene disorders that manifest in childhood. Colette and Christopher, the case study exemplar couple at high risk for transmitting cystic fibrosis to their future offspring, are typical of couples who use PGD for this application. Other examples of single gene disorders for which couples often opt to use PGD are hemoglobin disorders (e.g., β-thalassemia and sickle cell), Fragile X syndrome (i.e., a mental impairment disorder associated with autism or “autistic-like” symptoms), muscular dystrophies (e.g., Duchenne muscular dystrophy, myotonic dystrophy and spinal muscular atrophy) and Charcot-Marie-Tooth (i.e., a neuromuscular disorder that causes varying degrees of muscle weakness, atrophy and decreased sensation) (Goossens et al., 2009; Preimplantation Genetic Diagnosis International Society, 2008).
An emerging application for PGD is to prevent genetic conditions that manifest in adulthood. Huntington’s disease and early-onset familial Alzheimer’s disease are examples of adult-onset genetic disorders in this category. A related application for PGD is for couples where one or both partners are at high-genetic-risk for transmitting cancer predisposition mutations, such as those found in BRCA1 or BRCA2 genes. In these instances, the genetic mutation doesn’t cause a specific disorder, but rather the mutation is thought to place offspring at significantly higher risk for specific cancers in the future. PGD for adult-onset genetic disorders has generated social and ethical debate; however, the Practice Committee of the Society for Assisted Reproductive Technology and the Practice Committee of the American Society for Reproductive Medicine (2008) have approved PGD for this use.
Although PGD shares a history and link to prenatal diagnosis, some applications for high-genetic-risk couples have moved beyond what is considered traditional prenatal diagnosis. In particular, couples who have an ill child have opted to undergo PGD with the hope that a human leukocyte antigen (HLA) matched embryo will develop. The resulting child can then be a source of stem cell transplantation to save an ill sibling. PGD for HLA matching can be completed for this application alone, or a growing trend is to complete the HLA matching in conjunction with testing to prevent an identified genetic disorder such as Fanconi’s anemia, a blood disorder that often damages all body systems and carries a propensity for developing acute myeloid leukemia at an early age in affected individuals. The popular novel by Jodi Picoult (2004), My Sister’s Keeper, depicts the fictional life experience of one family, post-PGD use, where a child was purposefully conceived to save the life of an ill child.
Other applications for PGD are those in which one or both partners have an identified or known chromosomal translocation or other chromosomal rearrangement that places them at high risk for transmitting an unbalanced chromosomal complement to the embryo. Examples here include couples with known Robertsonian translocations or reciprocal translocations, inversions and insertions. In these instances, PGD significantly reduces the risk of miscarriage (to < 20 percent) and significantly increases the likelihood of a live birth (Practice Committee of the Society for Assisted Reproductive Technology and the Practice Committee of the American Society for Reproductive Medicine, 2008). This application differs from a subcategory of PGD that emerged and is known as preimplantation genetic screening, or PGS (see Box 3).
Box 3. Preimplantation Genetic Diagnosis (PGD) Versus Preimplantation Genetic Screening (PGS)
In PGD, high-genetic-risk couples enter into the procedure with the goal of preventing or identifying a known genetic disorder or mutation such as cystic fibrosis or a Robertsonian translocation. This differs fundamentally from PGS, an established derivative form of PGD. In PGS, the goal is to screen embryos for chromosomal aneuploidy (i.e., too many or too few chromosomes) to enhance the chance of establishing a viable pregnancy and healthy child. PGS is often used by couples in which the female partner is of advanced reproductive age and already undergoing in vitro fertilization (IVF), by couples with a history of repeated early miscarriage or failed IVF cycles and in instances where severe male factor infertility is recognized (Harper et al., 2008). Conflicting scientific data have been reported on whether or not PGS is beneficial (Schoolcraft, Katz-Jaffe, Stevens, Rawlins, & Munne, 2009; Verlinsky et al., 2005) while PGD has been accepted as a primary prevention measure and a major scientific advance (Practice Committee of the Society for Assisted Reproductive Technology and the Practice Committee of the American Society for Reproductive Medicine, 2007). What is clear surrounding PGS use is that establishing effective methods for embryo vitality assessment and screening is critical, and work in this area is ongoing (Harper et al., 2008; Vanneste et al., 2009; Wells, Alfarawati, & Fragouli, 2008). Given that two distinct application groups have emerged—PGD and PGS—health care providers need to be clear when communicating information about PGD to high-genetic-risk couples so that the subtle differences between PGD and PGS are understood.
PGD consists of multistage and complex procedures that include in vitro fertilization (IVF), cell biopsy, genetic analysis and embryo transfer. In the United States and worldwide, these procedures are often completed at specialized fertility clinics or PGD centers that have established access to health care providers with expertise in reproductive endocrinology and genetics. In order for PGD to take place, it’s necessary for fertile couples to undergo IVF, including the prerequisite components of ovarian hyperstimulation and oocyte extraction, to allow access to fertilizing oocytes or developing embryos from which the genetic material can be obtained. After the appropriately developed oocytes and embryos are obtained, a cell biopsy must take place to access the genetic material. Cell biopsy often occurs through a puncture in the zona pellucida by mechanical, chemical or laser procedures to gain access into the cell. The biopsy is performed on polar bodies, blastomere or blastocyst cells from which the genetic material is obtained. Thus, the biopsy is typically performed either immediately following fertilization on the oocyte polar bodies, or on day 3 embryos or on day 5 to day 6 embryos.
Oocyte or polar body biopsy is the preferred method at some specialized fertility clinics or PGD centers. Polar bodies are the products of female meiosis as oocytes undergo maturation and fertilization. Oocyte testing is often used for maternally derived autosomal dominant genetic disorders. This method only provides information on the maternal genetic material and infers the genetic makeup of the oocyte and resulting embryo; therefore, it cannot be used to detect genetic mutations that are only paternal in origin. It may, however, be more acceptable to some couples who have religious or ethical concerns regarding embryo manipulation because the genetic information is obtained at the zygote stage, before embryo formation.
Until recently, most clinics or PGD centers in the United States performed the embryo (blastomere) biopsy at the cleavage stage on day 3 after fertilization (Renwick & Ogilvie, 2007). This is typically the method of choice for paternally derived autosomal dominant genetic disorders and translocations as well as HLA typing (Kuliev & Verlinsky, 2005). In this cell biopsy method, typically one blastomere is removed from the cleavage stage embryo to provide nucleic material for the genetic analysis.
An emerging cell biopsy method for embryos is to complete the biopsy at the blastocyst stage on day 5 or day 6 after fertilization. This method has the advantage of removing two to nine trophectoderm cells, thereby allowing more cells for genetic analysis while leaving the integrity of the inner cell mass, which develops into the embryo, intact. Due to the difficulty in extending the culturing time of human embryos and because same-day genetic analysis is required, blastocyst biopsy is currently used in only a few PGD centers; however, current research in this area is ongoing (Basille et al., 2009; Renwick & Ogilvie, 2007).
It’s important to note that there are limits to the amount of genetic material that is available and that can be removed from oocytes or embryos without causing harm. Therefore, PGD for high-genetic-risk couples requires upfront knowledge about the couple’s specific genetic mutation or marker associated with the couple’s high-risk status. Couples typically submit buccal samples to the PGD laboratory prior to undergoing PGD to obtain the couple’s precise genetic mutation or marker to enhance and confirm the genetic analysis. For example, buccal samples obtained from Colette and Christopher would be used to purify their DNA and to confirm specific genetic markers on their genes before and after the mutation, delta-F508.
Once the genetic material is obtained through biopsy, genetic analysis can take place. In this stage, experts in nucleic analysis perform various molecular techniques. For single gene disorders such as cystic fibrosis, polymerase chain reaction (PCR) analysis is performed to allow amplification of specific DNA sequences for detecting gene mutations and hence genetic disorders. When PCR analysis is undertaken, an additional procedure of intracytoplasmic sperm injection is required to fertilize the oocyte(s) during IVF to obtain a clean genetic sample and avoid nucleic contamination from the sperm.
Fluorescent in situ hybridization (FISH) analysis is another molecular genetic analysis technique that is used to detect chromosomal abnormalities and chromosomal translocations. FISH analysis can also be used for sex chromosome analysis for X-linked disorders. Newer techniques in molecular genetics that hold promise for PGD include comparative genomic hybridization and microarray technology combined with embryo fingerprinting. These techniques may allow for an even greater number of genetic disorders to be diagnosed with increased accuracy and may also allow for an ability to evaluate all chromosomes of the embryo during a single procedure (Basille et al., 2009; Wells et al., 2008).
With the present techniques, misdiagnosis, although rare, is possible. The estimated risk of mistakenly identifying an embryo as normal when it does in fact have the genetic disorder (i.e., misdiagnosis) is about 2 percent for recessive disorders and up to 11 percent for dominant disorders (Lewis, Pinêl, Whittaker, & Handyside, 2001). The possibility of misdiagnosis has led to recommendations that PGD be followed by traditional prenatal diagnosis to confirm the PGD results (Practice Committee of the Society for Assisted Reproductive Technology and the Practice Committee of the American Society for Reproductive Medicine, 2008).
After the genetic analysis is complete, one or two embryos that are identified as unaffected or free of the genetic disorder are transferred into the female partner’s uterus under sterile conditions. Pregnancy rates for IVF with PGD vary, and no comprehensive national statistics are currently available for the United States. In general, couples can expect about a 21 percent success rate according to the ESHRE PGD consortium data (Goossens, et al., 2009). However, some clinics in the United States have reported success rates as high as 35 percent to 47 percent (Tur-Kaspa, Aljadeff, Rechitsky, Grotjan, & Verlinsky, 2010). It’s possible that no embryos may be available for transfer because all available embryos may have been identified as affected with the genetic disorder. It’s also possible that the genetic analysis may have been inconclusive or unable to determine with accuracy whether or not the embryo is unaffected or affected. Likewise, it’s also possible that a surplus number of healthy embryos will be identified. In this situation, couples are encouraged to freeze extra embryos for future use.
Nurses, advanced practice nurses and other frontline health care providers are critical in providing accurate information, education and anticipatory guidance about PGD to high-genetic-risk couples. Nurses and other health care providers can also assist couples by anticipating ethical concerns and supporting research surrounding PGD use. Couples similar to Colette and Christopher, who are curious about PGD, require multiple levels of support including baseline information and education of intricate and complex assisted reproductive and genetic information to understand the growing reproductive options that are available.
Information and Education
Several expert practice and scientific groups have developed recommendations and guidelines to optimize care for couples surrounding PGD use that is amenable to nursing care. Soini and colleagues (2006) recommend that providers take adequate time and personalize care during the educational process to ensure that couples are well-informed of PGD procedures. For example, high-genetic-risk couples need to understand that although they may be fertile, IVF is a necessary part of using PGD. Nurses and other providers should also be astute to the language used in educational exchanges, as couples may be easily confused by medical terms or jargon. Other experts (Jones, 2000; Kuliev & Verlinsky, 2005) have recommended that information and education include a discussion of the benefits and limitations of PGD (see Box 4).
Box 4. Benefits and Limitations of PGD
BENEFITSLIMITATIONS
  • Maximizes potential for genetically healthy child
  • Avoids anguish surrounding the decision to terminate an affected pregnancy
  • Optimizes potential for life-long parenthood
  • Reduces the potential for childhood hospitalizations and thereby decreases pain and suffering
  • IVF is a prerequisite to performing PGD even among fertile couples
  • Pregnancy success rates for IVF with PGD can be lower than when IVF is performed alone
  • Technical difficulties may occur during the PGD analysis and although rare, are possible
  • Financial cost is significant and often not covered by insurance
Couples have reported numerous benefits, including avoiding the anguish of terminating a pregnancy and a strong willingness to avoid pain and suffering in their future child (Hershberger & Pierce, 2010). The limitations of PGD should be discussed with the couple, too. These include informing the couple about the possibility of misdiagnosis and also the possibility that genetic mutation-free embryos may not be identified. In addition, the cost of undergoing IVF with PGD in the United States varies, but is estimated at about $10,500 to $21,000 (Galpern, 2007; Omurtag, Styer, Session, & Toth, 2009; Tur-Kaspa et al., 2010) and may be insurmountable for many couples (for further discussion and more detailed information about PGD, see the resources listed in Box 5).
Box 5. Resources
BOOKS & REPORTSWEB SITES
Atlas of Preimplantation Genetic Diagnosis, 2nd Edition, by Yury Verlinksy and Anver Kuliev. Abingdon, UK: Taylor and Francis Group, 2005.
Genetics/Genomics Nursing: Scope and Standards of Practice, by American Nurses Association and the International Society of Nurses in Genetics. Silver Spring, MD: Nursebooks.org, 2007.
IVF for PGD and PGD to Improve ART Outcome: 2009 American Society for Reproductive Medicine Postgraduate Course Syllabus (Course 19, 2009), by Yury Verlinksy, Ilan Tur-Kaspa and Luca Gianaroli, in cooperation with the Preimplantation Genetic Diagnosis Special Interest Group. Atlanta, GA: American Society for Reproductive Medicine, Atlanta, Georgia, 2009. Available at www.asrm.org/ASRM_Store
Nursing Care in the Genomic Era: A Case- Based Approach, by Jean Jenkins and Dale Lea. Sudbury, MA: Jones and Bartlett, 2005.
Preimplantation Genetic Diagnosis, 2nd Edition, by Joyce Harper. Cambridge, UK: Cambridge University Press, 2009.
Preimplantation Genetic Diagnosis: A Discussion of Challenges, Concerns, and Preliminary Policy Options Related to the Genetic Testing of Human Embryos, by Susannah Baruch, Gail Javitt, Joan Scott and Kathy Hudson. Washington, DC: Genetics and Public Policy Center, 2004. Available at: www.dnapolicy.org/pub.reports.php
American Society for Reproductive Medicine:
Nurses in Reproductive Medicine Professional Group
www.npg-asrm.org
IVF-Worldwide.com
www.ivf-worldwide.com/Education/preimplantation-genetic-diagnosis-pgd.html
International Society of Nurses in Genetics
www.isong.org
Preimplantation Genetic Diagnosis International Society
pgdis.org
As couples inquire about PGD, information and education on other available reproductive options for high-genetic-risk couples, such as natural conception, adoption, gamete donation or traditional prenatal diagnosis, should be included as well (Jones & Fallon, 2002; Practice Committee of the Society for Assisted Reproductive Technology and the Practice Committee of the American Society for Reproductive Medicine, 2008; Soini et al., 2006). Additional Web-based educational resources including information on support groups, genetic testing, counseling and an illustrated genetic glossary, can be found in Box 6.
Box 6. Online Educational Resources for Nurses and High-Genetic-Risk Couples
Genetic Testing and Counseling
Source: National Institutes of Health (NIH)
Information from the NIH addressing genetic testing and genetic counseling, ethics, research, and frequently asked questions about genetic testing.
health.nih.gov/topic/GeneticTestingCounseling
GeneTests
Source: University of Washington, Seattle
Updated and detailed information on genetic disorders, education, and counseling resources including an illustrated genetic glossary.
www.ncbi.nlm.nih.gov/sites/GeneTests/?db=GeneTests
IVF Connections
Source: Patient managed website
This supportive community provides education and opportunities for communication and improving coping skills among couples considering or undergoing IVF or PGD.
www.ivfconnections.com
Telling Stories
Source: National Genetics Education and Development Centre in the United Kingdom
Personal storytelling is encouraged and used to promote understanding of genetic disorders among healthcare providers.
www.tellingstories.nhs.uk/index.asp
Anticipatory Guidance and Referral
Frontline providers should communicate with couples and when appropriate, refer couples to genetic counselors, reproductive endocrinologists or other specialized providers in genetics and assisted reproduction. It’s important for front line nurses who have developed a trusted professional relationship with couples to recognize that some couples may be uncomfortable with unfamiliar providers and surroundings and may need anticipatory guidance on managing a cadre of specialists (Wille, Weitz, Kerper, & Frazier, 2004). Referral to discuss PGD with other multidisciplinary professionals, such as social workers, psychologists and religious leaders may also be encouraged.
Ethical, Legal and Psychosocial Concerns
Nurses may need to address the initial ethical, legal and psychosocial concerns among high-genetic-risk couples surrounding PGD use. Foremost, couples may contemplate issues of eugenics regarding whether or not it’s appropriate for parents to determine aspects of a future child’s genetic composition (Kalfoglou, Scott, & Hudson, 2005). Couples may also be concerned about confidentiality and disclosure of genetic information to other family members, insurance companies and other payers and, at times, with themselves (Adamson, 2010; Wang & Hui, 2009). If couples opt to move forward with PGD, nurses and other health care providers will need to ensure that couples are fully informed about the benefits, risks and limitations of PGD (Jefford & Moore, 2008; Jones, 2000).
Research Surrounding PGD
Another important implication is the need for nurses to encourage and support research in the field. Especially significant is research that is aimed at understanding and answering challenging decision-making questions surrounding PGD use (Klitzman, Appelbaum, Chung, & Sauer, 2008). Nurses can assist in this effort by informing couples about ongoing research in this area and advocating for additional governmental and private research support.
Initially viewed as an early form of prenatal diagnosis, PGD for high-genetic-risk couples has evolved over the past two decades to become an established reproductive option that has moved beyond traditional prenatal diagnostic applications. However, PGD is invasive and composed of multiple complex procedures that require upfront education and counseling. Couples opting to use PGD will need to complete a multistep process that includes IVF, cell biopsy, genetic analysis and embryo transfer. Nurses, advanced practice nurses, and other health care providers at the front line of care who are well-informed about PGD can serve as critical communication links between high-genetic-risk couples and advanced genetic and reproductive providers.
Following their initial discussion about PGD with their nurse and midwife, Colette and Christopher met with a genetic counselor and a women’s health nurse practitioner who specializes in reproductive endocrinology and infertility. They also discussed PGD in-depth with their religious leader. After carefully considering several reproductive options, including natural conception and prenatal testing with possible pregnancy termination, gamete donation, adoption, and even not having any more children, they decided to try IVF with PGD to conceive with a healthy baby.
BOTTOM LINE
  • PGD allows couples the ability to find out important genetic information about their embryos prior to establishing a pregnancy.
  • The number of genetic disorders for which PGD can be used is estimated at 170, and is steadily rising.
  • Nurses who are well-informed about PGD can serve as critical communication links between high-genetic-risk couples and advanced genetic and reproductive providers.
Box 2. PGD Applications for High-Genetic-Risk Couples
APPLICATIONGENETIC EXAMPLES*

X-Linked DisordersDuchenne muscular dystrophy
Fragile X syndrome
Hemophilia A

Single Gene DisordersRecessive Disorders
β-Thalassemia
Cystic fibrosis
Spinal muscular atrophy
Dominant Disorders
Charcot-Marie-Tooth
Marfan syndrome
Myotonic dystrophy

Adult-Onset DisordersHuntington’s disease
Familial Alzheimer disease

Cancer Predisposition DisordersFamilial adenomatous polyposis (APC Mutation)
Inherited breast and ovarian cancer (BRCA1 Mutation)

HLA Matching with Identification of a Genetic DisorderHLA matching and Fanconi’s anemia
HLA matching and X-Linked adrenoleukodystrophy

Identified Chromosomal RearrangementsRobertsonian translocation
Reciprocal translocation
*Note: Some individual genetic examples may apply to several “Application” categories
Acknowledgments
We thank the National Institutes of Health (NIH), National Institute of Nursing Research (R03 NR010351), National Institute of Child Health and Human Development and the Office of Research on Women’s Health (K12 HD055892) for support of this work. The information and case study exemplar presented here are the authors’ construction and do not necessarily represent the official views of the NIH or any particular individual or family. We would also like to acknowledge and thank the many nurses, midwives and nurse practitioners who encouraged us to write this article.
Footnotes
The authors report no conflicts of interest or relevant financial relationships.
Contributor Information
Patricia E. Hershberger, Assistant professor and NIH BIRCWH Faculty Scholar at the University of Illinois at Chicago College of Nursing and College of Medicine in Chicago, IL.
Catherine Schoenfeld, Clinical instructor at the University of Illinois at Chicago College of Nursing and a practicing certified nurse midwife at the University of Illinois at Chicago.
Ilan Tur-Kaspa, Founder and medical director of the Institute for Human Reproduction, the director of the IVF-PGD Program at the Reproductive Genetics Institute in Chicago, and a clinical professor at the Department of Obstetrics and Gynecology at the University of Chicago in Chicago, IL.
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