Series

Preimplantation Genetic Diagnosis: A Family Choice

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Preimplantation Genetic Diagnosis Can Stop Inherited Disease in a Family

02 Jul 2014

In 1998, Jennifer Leyton’s mother was dying of Huntington’s disease, an incurable neurologic disorder that robs people of movement and thought. Because the huntingtin mutation is autosomal-dominant, Leyton knew she had a 50 percent chance of having inherited it.

Leyton was young and wanted children, but she was determined not to take the chance of passing on Huntington’s to the next generation. She turned to what was then a rare technique—preimplantation genetic diagnosis (PGD). In this procedure a woman undergoes in vitro fertilization, then doctors test the resulting embryos for the mutant gene and implant only those that do not carry it. Leyton searched far and wide before she found a clinic, the Genetics & IVF Institute in Fairfax, Virginia, that could do this for her. She did not know if she herself carried the disease gene and wanted to keep it that way, so her doctor’s promise not to reveal her status was a key factor. Leyton and her husband traveled regularly from their home in New York City for the procedures. She endured physical ordeals associated with IVF, such as mood swings and bloating from taking hormones, and pain from having eggs harvested. The first attempt failed, but on the second try, Leyton became pregnant and eventually gave birth to healthy twins, a boy and girl, who are now 14.

For Leyton, all the trouble was worth it. “Yes, it was painful and hard on my body. It was expensive. But that doesn’t matter. What matters is I know my children will never, ever have this gene,” she told Alzforum.

Leyton’s story is becoming more common. Most fertility clinics in developed countries now offer PGD, and thousands of couples have used it to avoid passing on genes for serious disorders. (PGD is different from the experimental, and controversial, “three-parent” technique being tried to avoid passing on flawed mitochondrial DNA. That method was profiled June 30 in The New York Times.) In surveys, a majority of couples at risk for severe genetic diseases indicate they prefer PGD to getting prenatal testing later via amniocentesis and facing the wrenching decision of whether to terminate a pregnancy (see Musters et al., 2010). However, the use of PGD for adult-onset neurological disorders remains quite limited. Only a small percentage of Huntington’s families have used it, and a mere handful of families with Alzheimer’s genes are known to have done so. Mainly, this is because few people with autosomal-dominant AD have heard of this technique or realize it is an option for them, according to those in the field.

The expense and difficulty of the procedure deter some people. Others do not realize they can get PGD without having to find out whether they carry the disease gene themselves. Having a mother or father with a familial AD mutation can be enough to qualify for PGD. Alzforum contacted about a dozen families with autosomal-dominant AD, and once they heard about this option, many expressed tremendous interest.

“I have already lost six family members [to AD], and two of my three children will be added to that list. I would love it if my grandchildren had the chance to stop this in our family,” one anonymous commenter whose family carries a presenilin mutation wrote in an FAD support group discussion.

Society as a whole has just begun to grapple with the implications of this technology. Some ethicists have raised concerns about PGD for diseases that begin in middle age. People with familial AD or mutant huntingtin genes can enjoy 30 to 50 years of healthy life, and it is not fair to deny that life to embryos carrying the gene, these ethicists argue. However, most reproductive-medicine societies support the use of PGD to prevent serious adult-onset conditions. In 2012, the European Court of Human Rights ruled against restrictions in Italy that had banned fertile couples from using the procedure for disease prevention.

Some researchers believe PGD could be an effective way to combat inherited neurological disorders. “If people were aware of this and prepared to do it, we could get rid of the early onset dominant diseases in a generation,” said neurogeneticist John Hardy at University College London.

This two-part series provides an overview of PGD with perspectives from people who have taken advantage of it. Today’s story covers the history of the technology and how it is used; part two will describe some considerations that go into the decision to use PGD. 

PGD From Past to Present
PGD was first described in London in 1990 as a way to avoid passing on X-linked hereditary diseases (see Handyside et al., 1990). The procedure can be performed only in conjunction with in vitro fertilization. After doctors harvest eggs from the mother and fertilize them in a dish, they remove a few cells from the embryos for testing. About 90 percent of clinics do this on day three, when the embryos are at the six- to eight-cell stage. A few clinics wait until day five, when the embryo has become a blastocyst with an outer layer of trophectoderm cells that later form the placenta. In this case, clinicians remove trophectoderm cells for testing. Some evidence suggests this latter method has a lower chance of disrupting the embryo’s development (see Scott et al., 2013). Fertility clinics often send these biopsies to a separate genetics lab for analysis, meanwhile freezing the embryos to await the results. 

In another variation, clinicians can test the mother’s eggs by looking at polar bodies. These are discarded DNA from the meiotic cell division that generates the haploid egg. Polar bodies remain stuck to the egg until fertilization, when they degenerate. If the haploid polar body contains the disease gene, doctors can infer that the egg retained the other, healthy gene (see Verlinsky et al., 1990). This method only works if the mother is the at-risk parent. 

Once the presence of healthy embryos is confirmed, doctors discuss with their patients whether to implant one or two into the mother’s uterus. In the past, clinics often recommended two, but many centers now believe that a single-embryo pregnancy has a greater chance of success, said genetic counselor Margo Grady at Generations Fertility Care in Madison, Wisconsin. About 30 percent of embryo transfers result in a pregnancy, and about 80 percent of those pregnancies go to term, according to data collected by the European Society of Human Reproduction and Embryology (ESHRE) PGD Consortium (see Harper et al., 2012). These babies are as healthy as babies born through standard IVF procedures, the consortium reported.

Use of PGD has grown steadily over the past two decades. In the United States, about 5 percent of IVFs now involve such screening, according to data from the American Society for Reproductive Medicine. ESHRE figures indicate that about three-quarters of PGD procedures worldwide are done in older mothers to check that the number and shape of chromosomes are normal, or in families with known chromosomal translocations. Another 20 percent are done to screen for one of more than 200 single-gene or X-linked diseases. Data collected by ESHRE from 87 centers, the majority located in Europe, recorded about 1,600 uses of PGD for single-gene disorders in 2009, the latest year for which data has been published (see Moutou et al., 2014). The ESHRE PGD Consortium represents only a small portion of fertility clinics worldwide that use the technique, implying that actual numbers could be much higher, noted Veerle Goossens, who oversees data collection at ESHRE. 

Adult-Onset Diseases Lag Behind
Most often, families request PGD to test for diseases that manifest early in life, such as the blood disorder β thalassemia, cystic fibrosis, or spinal muscular atrophy. Its use remains rare for adult-onset neurological disorders. There, the main application is Huntington’s disease, with ESHRE data recording 136 PGD uses in 2009, and a total of 530 between 1997 and 2007. At typical success rates, this would translate to perhaps 200 to 300 children born free of the disease in this manner since 1997—a drop in the bucket compared with the total burden of Huntington’s disease. About 30,000 people in North America alone have HD, with another 150,000 estimated to be at risk of carrying the huntingtin gene repeats. These numbers are according to the Huntington Study Group, an organization of clinical researchers based in Rochester, New York. 

PGD for familial AD occurs even less often. The Reproductive Genetics Institute, a private PGD laboratory in Chicago, in 2002 published the first report of use by a 30-year-old woman with an APP mutation (see Verlinsky et al., 2002). Her child is now 13 years old, but RGI declined a reporter’s request to mediate an interview with the parents. Since 2002, RGI has used the technique to help families with autosomal-dominant AD give birth to six more unaffected children, Anver Kuliev at the institute wrote to Alzforum. Most clinics Alzforum contacted said they have never treated a couple with an AD gene, though Murali Doraiswamy at Duke University, Durham, North Carolina, was involved in a recent case. There is no record of PGD being used for Alzheimer’s in the ESHRE database, Goossens wrote. 

Frontotemporal dementias (FTDs) and amyotrophic lateral sclerosis (ALS) can also be inherited in autosomal-dominant fashion, but even fewer people at risk for these diseases have tried PGD. Kuliev told Alzforum that RGI has worked with one person at risk of an ALS gene, and that person delivered a healthy child; Kuliev is currently working with two more prospective parents from families with ALS. Brad Dickerson at Massachusetts General Hospital, Boston, runs a large clinic for frontotemporal dementia. Dickerson knows of three young women who inherited an FTD gene and used PGD to have unaffected children. Most clinics have never seen a case, however. The GIVF Institute that treated Leyton said they have never had a person at risk for FTD, ALS, or AD even inquire about PGD.

The scientific literature contains one published report of five mutation-free babies born through PGD and IVF to South Korean families carrying mutations for the neurological disease Charcot-Marie-Tooth (see Lee et al., 2013).

Clinicians and counselors who work with families at risk of these diseases say that most are simply unaware that PGD exists as an option. In many cases, primary care physicians and neurologists do not tell them about it. A recent survey of U.S. internists found that only 5 percent had ever recommended PGD to a patient, and only 7 percent felt qualified to answer patients’ questions about the procedure (see Klitzman et al., 2013). Neurologists typically do not have this issue on their radar, Dickerson noted. Doraiswamy recently argued that the time has come for neurological societies to consider developing guidelines to help their members talk to patients about PGD (see Tur-Kaspa et al., 2014). A group of geneticists, psychologists, and ethicists in the Netherlands and Belgium recently formulated recommendations for good clinical practice in the care of families facing this issue (see de Die-Smulders et al., 2013).

Neurologist Samuel Frank at Boston University told Alzforum that perhaps one-quarter of the HD patients he sees know about PGD, and most of them found out about it on their own by searching the Internet. Many of the first families to use PGD for neurological diseases came from highly educated or medical backgrounds. A survey of families in Portugal who carry a hereditary neuropathy found that those who knew about PGD tended to be younger and have higher incomes than those who did not (see Valdrez et al., 2014). Dickerson said that the women with FTD genes who used PGD found out about it because their families were involved in research studies. Some advocacy groups spread the word among their members; for example, the Huntington’s Disease Society of America holds presentations on PGD at their annual conference.

Most of the familial Alzheimer’s community remains in the dark about this procedure. When PGD was presented to a familial AD support group in London in February 2013, most had never heard of it. In a follow-up conversation in 2014, group members expressed that they wished they had known about this option before they had their children. “I definitely would have looked into testing,” wrote one commentator. “Now my two children each have a 50 percent chance. It breaks my heart.”—Madolyn Bowman Rogers.

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References

Paper Citations

1. Musters AM, Twisk M, Leschot NJ, Oosterwijk C, Korevaar JC, Repping S, van der Veen F, Goddijn M. Perspectives of couples with high risk of transmitting genetic disorders. Fertil Steril. 2010 Sep;94(4):1239-43. Epub 2009 Oct 7 PubMed.
2. Handyside AH, Kontogianni EH, Hardy K, Winston RM. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature. 1990 Apr 19;344(6268):768-70. PubMed.
3. Scott RT Jr, Upham KM, Forman EJ, Zhao T, Treff NR. Cleavage-stage biopsy significantly impairs human embryonic implantation potential while blastocyst biopsy does not: a randomized and paired clinical trial. Fertil Steril. 2013 Sep;100(3):624-30. Epub 2013 Jun 15 PubMed.
4. Verlinsky Y, Ginsberg N, Lifchez A, Valle J, Moise J, Strom CM. Analysis of the first polar body: preconception genetic diagnosis. Hum Reprod. 1990 Oct;5(7):826-9. PubMed.
5. Harper JC, Wilton L, Traeger-Synodinos J, Goossens V, Moutou C, SenGupta SB, Pehlivan Budak T, Renwick P, De Rycke M, Geraedts JP, Harton G. The ESHRE PGD Consortium: 10 years of data collection. Hum Reprod Update. 2012 May-Jun;18(3):234-47. Epub 2012 Feb 16 PubMed.
6. Moutou C, Goossens V, Coonen E, De Rycke M, Kokkali G, Renwick P, SenGupta SB, Vesela K, Traeger-Synodinos J. ESHRE PGD Consortium data collection XII: cycles from January to December 2009 with pregnancy follow-up to October 2010. Hum Reprod. 2014 May;29(5):880-903. Epub 2014 Mar 11 PubMed.
7. Verlinsky Y, Rechitsky S, Verlinsky O, Masciangelo C, Lederer K, Kuliev A. Preimplantation diagnosis for early-onset Alzheimer disease caused by V717L mutation. JAMA. 2002 Feb 27;287(8):1018-21. PubMed.
8. Lee HS, Kim MJ, Ko DS, Jeon EJ, Kim JY, Kang IS. Preimplantation genetic diagnosis for Charcot-Marie-Tooth disease. Clin Exp Reprod Med. 2013 Dec;40(4):163-8. Epub 2013 Dec 31 PubMed.
9. Klitzman R, Chung W, Marder K, Shanmugham A, Chin LJ, Stark M, Leu CS, Appelbaum PS. Views of internists towards uses of PGD. Reprod Biomed Online. 2013 Feb;26(2):142-7. Epub 2012 Nov 21 PubMed.
10. Tur-Kaspa I, Jeelani R, Doraiswamy PM. Preimplantation genetic diagnosis for inherited neurological disorders. Nat Rev Neurol. 2014 Jul;10(7):417-24. Epub 2014 May 27 PubMed.
11. de Die-Smulders CE, de Wert GM, Liebaers I, Tibben A, Evers-Kiebooms G. Reproductive options for prospective parents in families with Huntington's disease: clinical, psychological and ethical reflections. Hum Reprod Update. 2013 May-Jun;19(3):304-15. Epub 2013 Feb 1 PubMed.
12. Valdrez K, Silva S, Coelho T, Alves E. Awareness and motives for use and non-use of preimplantation genetic diagnosis in familial amyloid polyneuropathy mutation carriers. Prenat Diagn. 2014 Apr 17; PubMed.

External Citations

1. The New York Times
2. ruled against
3. data
4. Huntington Study Group

Further Reading

News

1. Families Fight Back As Disease Claws at Next Generation 15 Oct 2012
2. Data in Disguise: As Results Roll In, DIAN Works to Guard Privacy 12 Oct 2012
3. Study Finds Ways to Predict, Track Huntington’s Disease 17 May 2013
4. Finally, Therapies Targeting Huntingtin Poised for Clinic 24 May 2013
5. Time Is Ripe for Clinical Trials in Frontotemporal Degeneration 27 Dec 2011

Preimplantation Genetic Diagnosis: It’s No Walk in the Park

03 Jul 2014

When people learn that they carry a gene for a fatal neurological disorder, they fear not just for themselves, but for their children who might inherit the same condition. Some vow never to have biological children. This was the case for Amanda Kalinsky, who at the age of 26 found out that she carried the gene for Gerstmann-Sträussler-Scheinker (GSS) syndrome, an autosomal-dominant prion disease. She had watched her father, uncle, grandfather, and great-aunt die slow and painful deaths from GSS, and she swore she would not saddle her future children with the disease. Then a genetic counselor told her about preimplantation genetic diagnosis (PGD), in which doctors test embryos conceived in vitro for a disease gene and implant only those that are free of it. “I’d never heard of it before; my husband is a physician and he’d never heard about it before,” Kalinsky said. 

The counselor laid out the pros and cons, which included the warning that the process would be long, expensive, and arduous. Kalinsky and her husband thought about it for a couple of months before they decided to try it. “Genetic counseling really helped me,” Kalinsky said. “It should be mandatory for families considering this.” The Kalinskys now have 3-year-old twins and a year-old boy, who will never have to worry about having GSS. The New York Times told the Kalinskys' story on Feb. 3, and the case was written up in JAMA Neurology (see Tur-Kaspa et al., 2014).

Kalinsky has no doubt about her choice. “I would do it a million times over. When you get a diagnosis like this, you feel helpless. This is a way of fighting back and stopping the disease from passing to the next generation,” she told Alzforum.

With the increasing availability of PGD, more families will soon face the same choice the Kalinskys did. While many are intrigued by the promise of pruning fatal genes out of their family tree, they have to weigh this benefit against the procedure’s difficulties. This story lays out issues families confront as they decide what to do.

The Kalinsky children. Image courtesy of Amanda Kalinsky.

Costs and Stress Loom Large
The price tag presents a barrier to most families. In the United States, IVF for fertile couples is typically not covered by insurance, except in Massachusetts and Illinois. The cost of IVF and PGD varies by state. In Madison, Wisconsin, genetic counselor Margo Grady at Generations Fertility Care estimated the out-of-pocket price of one IVF cycle at about $12,000, and PGD adds another $3,000. Grady noted that she often gets insurers to cover the PGD portion, but not IVF. In New York City, IVF plus PGD runs about $25,000, said genetic counselor Jill Goldman at Columbia University. Since not all IVF cycles lead to a pregnancy, the expense can mount quickly. In Europe, the procedure is more likely to be covered by insurance, but it depends on the country. In Spain, Denmark, and the United Kingdom, PGD is covered only at public clinics; in much of Eastern Europe, it is not covered at all (see 2010 report by the European Society of Human Reproduction and Embryology PGD Consortium).

Several genetic counselors told Alzforum that cost is the primary deterrent. Grady said many couples initially express interest, but quickly bow out when they hear the price. Fewer than 5 percent of couples she speaks with go on to do it. In Massachusetts, where the procedure is covered, rates are much higher. Irene Souter, director of the PGD program at Massachusetts General Hospital Fertility Center, estimated that about half of the Huntington’s disease families her clinic counsels about the procedure eventually try it.

Beyond the financial burden, the invasive nature of PGD—and IVF in general—discourages some families. In IVF, women must take hormones and other drugs to stimulate the maturation of multiple eggs and prepare the uterus for a pregnancy, then their eggs must be harvested from their ovaries with a needle. There is no study that shows IVF has a lasting negative impact on the body, but subjectively women perceive it as quite grueling. Kalinsky said the hormones pitched her into huge emotional swings. “I went a little bit crazy,” she said. That ended once she stopped the treatment.

Some families are loath to “medicalize” their family planning. One young man whose father has the presenilin 1 gene told Alzforum, “I was happy to hear [PGD] was a possibility, but it definitely adds some strain to know that this is the way I’m going to have to approach a sacred thing such as having a baby. That it has to be planned out in advance and done in such a responsible way.”

Genetic counselors also caution families that, like any medical test, embryo testing carries a small chance for misdiagnosis. Carrie Koval, a genetic counselor at New York-Presbyterian Hospital, said she tells patients that the procedure dramatically cuts the risk that an embryo will carry a dominant gene, from 50 percent to about 2 percent. ESHRE data from 1997 to 2007 report a lower misdiagnosis risk, of about 0.5 percent (see Harper et al., 2012). Counselors suggest that if families want to be absolutely certain they won’t pass on a disease gene, they should get prenatal testing as well.

The Right Not To Know: Non-Disclosure PGD
Many people at risk of an inherited neurological disease do not want to know whether they have the gene. Goldman estimated that fewer than one in five people at risk for HD or early onset AD want to be tested. Most fertility clinics offer “non-disclosure PGD,” where clinic personnel withhold gene status from the prospective parents. To avoid leaking any clues, doctors do not tell the family how many eggs were retrieved or fertilized, or what percent were healthy. They perform IVF regardless of whether the at-risk parent carries the gene, hence that parent need not undergo predictive genetic testing as a prerequisite for PGD.

Non-disclosure PGD requires specialized protocols and attention to detail, Grady told Alzforum. She recommends that interested couples select a clinic that does the procedure regularly. A recent publication spells out recommended best practices for this method (see Tur-Kaspa, 2012).

Some clinics also offer a variation called exclusion testing, in which even clinic personnel do not find out whether the at-risk parent carries the gene. Instead, geneticists analyze markers from the region of the chromosome around the disease gene, and select only embryos that inherited those markers from the unaffected grandparent of the parent at risk. This option requires DNA testing of the grandparents, and also means that some healthy embryos with the normal gene from the affected grandparent would be discarded.

While there are no exact figures for how many couples choose non-disclosure or exclusion testing, Koval estimates that a quarter of the Huntington’s families she sees opt to be tested. Data from Europe indicate that about one-third of couples at risk for HD chose this option between 1995 and 2008 (see Van Rij et al., 2012). 

The decision to know or not is highly personal. Jennifer Leyton, who watched her mother die from Huntington’s, chose not to learn her status when she got pregnant through PGD. “I just wanted to live my life,” she told Alzforum. Kalinsky made the opposite decision. “For me, living in the unknown is worse than living in the known,” she said. But she believes that the availability of non-disclosure PGD represents a wonderful option for families. “Knowing your results is a life-changing thing, and it’s not for everybody,” she said.

On average, about half the couples who choose non-disclosure PGD and IVF for dominant diseases do not carry the disease gene. For this reason, some countries in Europe, including the Netherlands, have balked at covering this procedure (see Asscher and Koops, 2010). 

Ethics of PGD
In Europe, regulations on the use of PGD span the gamut. For example, Spain puts few restrictions on use; other countries, such as France and Germany, allow the procedure only for screening against severe genetic diseases; and a few, including Austria, Lithuania, and Latvia, ban it. Sex selection is forbidden throughout the European Union, but nonetheless about 2 percent of reported PGD cycles are done for this purpose, according to ESHRE data.

In the United States, the American Society for Reproductive Medicine has issued guidelines that support the procedure for severe, untreatable adult-onset conditions such as HD. The guidelines also recommend that PGD be allowed for less severe disorders, or genes that are not fully penetrant such as the breast cancer gene BRCA1. ASRM discourages the use of PGD for selecting a child’s sex. However, these guidelines are not binding. “There are no laws or regulations determining who may use PGD for what purpose,” Eleanor Nicoll at ASRM wrote Alzforum. For example, some U.S. clinics do offer sex selection for the purpose of balancing genders within a family.

In the absence of regulation, individual clinics are left to make their own decisions. “Anything that physicians are uncomfortable with we discuss as a group, and it goes through our ethics board,” Grady said. Her clinic has performed PGD to screen for risk genes of adult-onset illnesses such as BRCA1. “Generally, if it’s a serious disease, we welcome talking to people and setting up this process,” she said.

Some ethicists have raised questions about the use of the technology for adult-onset diseases. In 2002, when a woman who carried the V717L APP mutation first used PGD to conceive healthy children, some asked whether genetic technology should be used to help people who may not live to see their children reach adulthood become parents (see Towner and Loewy, 2002; 2002 AP news story). Others are troubled by the fact that embryos carrying a disease gene are discarded, albeit within a week of fertilization. Clinicians and counselors Alzforum spoke with believe this choice has to be left up to families. “I don’t think we can make that decision for them. Families with all kinds of diseases want to have children and do so successfully. They do need to plan for it and build their support system,” Goldman said.

Clinicians who have seen the devastation these diseases wreak on families believe the good outweighs the bad. “We’re not saying PGD should be done for sex selection or cosmetic traits or intelligence,” said Murali Doraiswamy at Duke University, Durham, North Carolina. “We are focusing on the fact that this technique is available for serious brain disorders that are inherited and often fatal. Every mother wants to give birth to a child who has the best chance at life.”

For couples from religious backgrounds, the choice may be wrenching. “To me, discarding embryos would be akin to abortion,” said one man whose father has the presenilin 2 gene. Nonetheless, he said if he had known about PGD before he had his children, he and his wife would have considered it. “We would have had to pray and talk to our pastor about it, but it would have been nice to have that option. Early onset Alzheimer’s is a terrible way to die.”

Families who have been through PGD say they struggled with the decision to discard affected embryos, but found it preferable to having to terminate a pregnancy. Jeff Carroll is a Huntington’s researcher at Western Washington University, Bellingham, who himself carries the gene for the disorder. He and his wife used PGD to have their twin boy and girl, who just turned eight. When they went through the procedure in 2005, PGD was rarely offered commercially, and methods were less refined than they are now. Doctors suggested that instead of PGD, the Carrolls use prenatal diagnosis such as chorionic villi sampling or amniocentesis and terminate an affected pregnancy. “We were uncomfortable with that,” Carroll told Alzforum.

He hopes that more families take up PGD to eliminate disease genes. “I’m glad I’m here. I’m glad that people of a previous generation had kids and carried on,” Carroll told Alzforum. “But we are a generation where this technology exists. It isn’t a cure for the generation alive today, but it’s a cure for the next generation. I think we owe it to them to use it as much as we can.”—Madolyn Bowman Rogers.

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References

Mutations Citations

1. APP V717L

Paper Citations

1. Tur-Kaspa I, Jeelani R, Doraiswamy PM. Preimplantation genetic diagnosis for inherited neurological disorders. Nat Rev Neurol. 2014 Jul;10(7):417-24. Epub 2014 May 27 PubMed.
2. Harper JC, Wilton L, Traeger-Synodinos J, Goossens V, Moutou C, SenGupta SB, Pehlivan Budak T, Renwick P, De Rycke M, Geraedts JP, Harton G. The ESHRE PGD Consortium: 10 years of data collection. Hum Reprod Update. 2012 May-Jun;18(3):234-47. Epub 2012 Feb 16 PubMed.
3. Tur-Kaspa I. Clinical management of in vitro fertilization with preimplantation genetic diagnosis. Semin Reprod Med. 2012 Aug;30(4):309-22. Epub 2012 Jun 21 PubMed.
4. Van Rij MC, De Rademaeker M, Moutou C, Dreesen JC, De Rycke M, Liebaers I, Geraedts JP, De Die-Smulders CE, Viville S, BruMaStra PGD working group. Preimplantation genetic diagnosis (PGD) for Huntington's disease: the experience of three European centres. Eur J Hum Genet. 2012 Apr;20(4):368-75. Epub 2011 Nov 9 PubMed.
5. Asscher E, Koops BJ. The right not to know and preimplantation genetic diagnosis for Huntington's disease. J Med Ethics. 2010 Jan;36(1):30-3. PubMed.
6. Towner D, Loewy RS. Ethics of preimplantation diagnosis for a woman destined to develop early-onset Alzheimer disease. JAMA. 2002 Feb 27;287(8):1038-40. PubMed.

External Citations

1. the Kalinskys' story
2. 2010 report
3. guidelines
4. 2002 AP news story

Further Reading

External Links

1. Early Onset Familial AD