Use Of Preimplantation Genetic Diagnosis Research Articles

Is a deaf future an "Open" future? Reconsidering the open future argument against deaf embryo selection.

One prominent argument against the use of preimplantation genetic diagnosis to select a deaf embryo with the aim of creating a deaf child is that it violates the child's right to an open future. This paper challenges the open future argument against deaf embryo selection, criticizing its major premise that deafness limits a child's opportunity range in ways that compromise their future autonomy. I argue that this premise is not justified and is supported by negative presumptions about deaf embodiments that are suspect and in need of further argumentation. First, available interpretations of the open future concept fail to justify the devaluation of deaf traits as inherently autonomy-diminishing. Second, arguing against deaf embryo selection requires demonstrating that a deaf trait generally constrains opportunity ranges independent of social context. But such analyses neglect important social and relational components of autonomy. For these reasons, merely appealing to the child's right to an open future does not sufficiently support the conclusion that deaf embryo selection is wrong.

Assessment of attitudes towards the use of preimplantation genetic diagnosis in a single center in Riyadh, Saudi Arabia.

In this cross-sectional study, we assessed the attitudes of the general public in Saudi Arabia regarding both medical and non-medical applications of pre-implantation genetic diagnosis (PGD). The study was conducted in King Abdullah Specialist Children's Hospital (KASCH) in Riyadh with a sample size of 377. Demographic information was collected, and attitudes towards applications of PGD were assessed using a pre-validated self-administered questionnaire. Out of the total sample size, 230 (61%) were males, 258 (68%) were married, 235 (63%) had one child or more, and 255 (68%) were older than 30 years of age representing the majority of participants. Only 87 (23%) of participants reported prior experience with PGD. Personally, knowing someone who had a prior experience with PGD was associated with higher attitude scores (more favorable attitudes towards PGD) (p-value = 0.04). The findings of this study indicate that our sample of Saudi individuals generally had a positive attitude towards the use of PGD.

Conception of Saviour Siblings: Religious Views in Malaysia.

The advancement of human reproductive technology has made it possible for parents with a child affected by a haematological disorder to select and bring into being, a prospective child who can act as a matched stem cell donor. This can be done through the use of preimplantation genetic diagnosis (PGD) coupled with human leukocyte antigen (HLA) typing (PGD-HLA typing), or HLA tying as a standalone procedure, where a healthy embryo, which is an HLA match to the existing sick sibling, is chosen for implantation. The creation of such a sibling (saviour sibling) is normally taken as a last resort when there is no related or unrelated matched donor. While the conception of a saviour sibling may serve as a reliable and realistic treatment option for the ailing child, it also poses new moral questions that challenge a religiously pluralistic society such as Malaysia. The use of PGD-HLA typing may be controversial as it involves creating a life to save a life, selection of compatible human embryos and destruction of the unselected embryos. At present, there is no legal framework regulating the conception of saviour siblings. The development of ethically sound and appropriate local laws and policies should consider the views of religious communities, especially when it involves a controversial subject such as the conception of saviour siblings. This article seeks to explore the perceptions of religious scholars and representatives of the major religions professed and practised in Malaysia, namely Islam, Buddhism, Christianity and Hinduism, through qualitative interviews.

Double heterozygosity for TP53 and BRCA1 mutations: clinical implications in populations with founder mutations.

The co-occurrence or double heterozygosity of pathogenic/likely pathogenic sequence variants (P/LPSVs) in major cancer susceptibility genes has rarely been reported. Such co-occurrence raises the issues of accurate genetic counseling, preferred recommended surveillance scheme, and the use of preimplantation genetic diagnosis (PGD). A clinical report of an Ashkenazi Jewish (AJ) family with co occurrence of two PSVs in BRCA1 and TP53 and a literature search. In an AJ family with a substantial history of cancer limited to the maternal side, two siblings co-harbored TP53 (c.733C>A; p.G245S) and the predominant 5266dup BRCA1 mutation, originating from the mother and the father, respectively. PGD is ongoing. Four families were thus far reported as double heterozygotes for both BRCA1/BRCA2 and TP53. Based on the limited available data, it seems that the phenotype in double PSV heterozygotes is not more severe than in single PSV carrier in either gene. This family highlights the need to genotype both parents, especially in populations with founder mutations, when a BRCA1 mutation is detected in an offspring, regardless of family history. The combination of mutations in these two genes presents a challenge for PGD since both genes are located on chromosome 17.

Mutations of the cystic fibrosis transmembrane conductance regulator gene in males with congenital bilateral absence of the vas deferens: Reproductive implications and genetic counseling (Review).

Congenital bilateral absence of the vas deferens (CBAVD) is predominantly caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CBAVD accounts for 2–6% of male infertility cases and up to 25% of cases of obstructive azoospermia. With the use of pre-implantation genetic diagnosis, testicular or epididymal sperm aspiration, intracytoplasmic sperm injection and in vitro fertilization, patients affected by CBAVD are able to have children who do not carry CFTR gene mutations, thereby preventing disease. Therefore, genetic counseling should be provided to couples receiving assisted reproductive techniques to discuss the impact of CFTR gene mutations on reproductive health. In the present article, the current literature concerning the CFTR gene and its association with CBAVD is reviewed.

Identification of novel microsatellite markers flanking GJB2 gene in order to use in preimplantation genetic diagnosis of hearing loss: A comparison of whole-genome amplification and semi-nested PCR

Hearing loss is the most prevalent sensorineural disorder which can be caused by genetic factors in more than half of the cases. GJB2 mutations with the frequency of 18.7% are the most common cause of autosomal recessive non-syndromic hearing loss (ARNSHL) in the Iranian population. The aim of the current study was to genotype 100 healthy individuals for eight microsatellite markers flanking the GJB2 gene, and to study markers on ten blastomeres using semi-nested PCR and Whole-genome amplification (WGA). All microsatellite markers within 1 Mb flanking the GJB2 gene were identified. From the identified markers, four with potentially high heterozygosity values were selected. The heterozygosity indices of four newly discovered markers and four previously reported markers were calculated. The markers and the GJB2 gene were also validated on single lymphocytes and blastomeres. Totally, 77 alleles were observed in eight loci. D13S046 showed the highest polymorphism and D13S141 showed the lowest. The observed heterozygosities of all markers, except D13S141, were higher than 50%. All single cells were genotyped successfully by the two techniques. Our findings indicate a high degree of polymorphism of the selected markers. Due to the high rate of successful amplification of markers in all ten blastomeres and the low level of allelic drop out (ADO), a combination of these eight microsatellite markers in conjunction with direct mutation detection is suggested for performing preimplantation genetic diagnosis (PGD) of hearing loss due to GJB2 mutations.

The need to address legal ambiguity on conceiving saviour siblings in Malaysia

Conceiving a saviour sibling can be a vital treatment option for a child suffering from a haematological condition. However, the legality of this option may be called into question in countries where there is no clear law or policy regarding the use of preimplantation genetic diagnosis with HLA typing (PGD-HLA typing) or HLA typing alone for this purpose. In Malaysia for instance, there is no legislative framework governing the use of assisted reproductive technology and the only guidance appears to be provided by guidelines issued by the Malaysian Medical Council. In the absence of clear direction, broad guidelines or policy positions taken by such statutory bodies may heavily influence the practice or roll out of certain technologically advanced therapeutic interventions.Previous literature has construed this Guideline narrowly as prohibiting this practice. This paper argues that the narrow and traditional interpretation method used in previous literature is wanting and suggests a more meaningful approach to the interpretation of the Guideline and advocates that this interpretative method should be applied in similar instances involving technologically advanced treatment modalities in other similar situations. Such guidance documents should be interpreted in a manner which takes into account the nature of the technology, its implications and intended use.

Preimplantation genetic diagnosis: What do BRCA mutation carriers think?

1526 Background: The use of pre-implantation genetic diagnosis (PGD) to select against BRCA mutated embryos for in-vitro fertilization (IVF), introduces complex choices for patients with pathogenic BRCA mutations. We sought to describe the uptake of and attitudes toward this technology in this patient population. Methods: We conducted a prospective survey study at a single institution in New York City affiliated with both a Cancer Center and Fertility Center, to assess attitudes and utilization of PGD. Cancer Center staff distributed surveys to patients with known BRCA mutations between April and August 2018. Survey participation was voluntary and anonymous. Survey data were analyzed using descriptive statistics and two-tailed t tests. Results: 80 survey responses were collected. A majority of the patient population identified as Caucasian (87.5%, 70) and Jewish (52.5%, 42). The survey was distributed to all age groups; however 81% (65) were between 26 and 45 years of age. 63.8% (51) had heard of PGD prior to completing the survey, while 36.3% (29) had not. Only 40% of respondents (32) felt sufficiently educated regarding PGD. 35% (28) patients met with an REI, of whom 6.3% (5) utilized IVF with PGD, and 21.3% (17) plan to use IVF with PGD in the future. 11.3% (9) wish they had known about this technology prior to starting a family, 20% (16) would not have used PGD had they known about it prior to childbearing. Reasons respondents were unlikely to pursue PGD included: cost (38.8%, 31), completed childbearing (25%, 20), medical risk (18.8%, 15), and ethical concerns (16.2%, 13). Patients gave cost estimates for PGD ranging from $500 - $120,000. There was no statistically significant correlation between likelihood of pursuing PGD and parity (p = 0.45), religion (p = 0.78), education level (p = 0.13), number of family members affected by BRCA mutations (p = 0.20) or by cancer (p = 0.11). Conclusions: Overall, a small number of patients with pathogenic BRCA mutations utilize PGD. A minority of survey respondents felt adequately educated about PGD. Reported barriers to uptake were varied, and there was a wide range of cost estimates reported. Our results suggest that increased patient education regarding PGD in BRCA mutation carriers is warranted.

The clinical application of preimplantation genetic diagnosis for X-linked retinitis pigmentosa.

To investigate the usefulness of preimplantation genetic diagnosis (PGD) based on mutated allele revealed by sequencing with aneuploidy and linkage analyses (MARSALA) for a pedigree with X-linked retinitis pigmentosa (XLRP). One pathogenic mutation (c.494G > A) of the retinitis pigmentosa GTPase regulator (RPGR) gene was identified in a pedigree affected by XLRP. Then, PGD was carried out for the couple, of which the wife was an XLRP carrier. Three blastocysts were biopsied and then MARSALA was performed by next-generation sequencing (NGS). Prenatal diagnosis was also carried out to confirm the PGD results. Three blastocysts were all unaffected. Then, one of the embryos was chosen randomly to be transferred, and the pregnancy was acquired successfully. The results of prenatal diagnosis were consistent with the PGD results. The fetus did not carry RPGR mutation (c.494G > A) and had normal chromosome karyotype. As a result, a healthy baby free of XLRP condition was born. The PGD method based on MARSALA was established and applied to a family with XLRP successfully. MARSALA will be a valid tool, not only for XLRP families but also for families affected with other monogenetic disorders, to prevent transmission of the genetic disease from parents to offspring.

Pre-implantation Genetic Diagnosis: The Road Forward in Canada.

The use of pre-implantation genetic diagnosis (PGD) is increasing as the list of indications it can test for constantly expands. This raises new challenges for clinicians and prospective parents regarding possible uses and calls for guidance. Policy approaches towards PGD vary greatly worldwide. The 2004 Canadian Assisted Human Reproduction Act does not provide guidance, except for prohibiting non-medical sex selection. Criminal legislation is an unsuitable policy instrument to regulate human genetics and reproductive medicine. We call for professional societies to issue guidelines regarding the uses of PGD that would establish the standard of care and legal norms. Such guidelines should be based on a patient-centered approach and respect individual autonomy in reproductive decision-making. Canadian approaches to PGD should also consider issues related to equity of access. Moreover, since PGD often raises concerns about eugenic uses, guidelines should also consider its societal impact and its implementation should be accompanied by policies that maintain or increase social support for people with disabilities. Finally, public engagement could provide an evidence-base regarding Canadian societal values and concerns that should guide regulatory reform, for example, the regulation of non-medical sex selection through PGD.

Use of preimplantation genetic testing for monogenic defects (PGT-M) for adult-onset conditions: an Ethics Committee opinion

Preimplantation genetic testing for monogenic diseases for adult-onset conditions is ethically permissible for a range of conditions including when the condition is serious and no safe, effective interventions are available. The Committee strongly recommends that a genetic counselor experienced with PGT-M counsel patients considering such procedures. This document replaces the document titled "Use of preimplantation genetic diagnosis for serious adult-onset conditions: a committee opinion," last published in Fertil Steril 2013;100;54-7.

Public Perceptions of Ethical, Legal and Social Implications of Pre-implantation Genetic Diagnosis (PGD) in Malaysia.

Pre-implantation genetic diagnosis (PGD) became well known in Malaysia after the birth of the first Malaysian 'designer baby', Yau Tak in 2004. Two years later, the Malaysian Medical Council implemented the first and only regulation on the use of Pre-implantation Genetic Diagnosis in this country. The birth of Yau Tak triggered a public outcry because PGD was used for non-medical sex selection thus, raising concerns about PGD and its implications for the society. This study aims to explore participants' perceptions of the future implications of PGD for the Malaysian society. We conducted in-depth interviews with 21 participants over a period of one year, using a semi-structured questionnaire. Findings reveal that responses varied substantially among the participants; there was a broad acceptance as well as rejection of PGD. Contentious ethical, legal and social issues of PGD were raised during the discussions, including intolerance to and discrimination against people with genetic disabilities; societal pressure and the 'slippery slope' of PGD were raised during the discussions. This study also highlights participants' legal standpoint, and major issues regarding PGD in relation to the accuracy of diagnosis. At the social policy level, considerations are given to access as well as the impact of this technology on families, women and physicians. Given these different perceptions of the use of PGD, and its implications and conflicts, policies and regulations of the use of PGD have to be dealt with on a case-by-case basis while taking into consideration of the risk-benefit balance, since its application will impact the lives of so many people in the society.

Comparative preimplantation genetic diagnosis policy in Europe and the USA and its implications for reproductive tourism.

Unlike many European nations, the USA has no regulations concerning the use of preimplantation genetic diagnosis (PGD), a technique employed during some fertility treatments to select embryos based on their genes. As such, PGD can and is used for a variety of controversial purposes, including sex selection, selection for children with disabilities such as deafness, and selection for ‘saviour siblings’ who can serve as tissue donors for sick relatives. The lack of regulation, which is due to particular features of the US political and economic landscape, has ethical and practical implications for patients seeking PGD around the world. This paper contrasts the absence of PGD oversight in the USA with existing PGD policies in Switzerland, Italy, France and the UK. The primary reasons why PGD is not regulated in the USA are addressed, with consideration of factors such as funding for assisted reproductive technology treatmemt and the proximity of PGD to the contentious abortion debate. The obstacles that would need to be overcome in the USA for PGD to be regulated in the future are outlined. Then, the significance of the current divergence in PGD policy for patients around the world are discussed. Regulatory differences create opportunities for reproductive tourism, which result in legal, health and moral challenges. The paper concludes with comments on the need for policymakers around the world to balance respect for the characters and constitutions of their individual countries with appreciation of the needs of infertile patients across the globe.

Reproductive Decision-Making in Women with BRCA1/2 Mutations.

Expanded genetic testing of BRCA mutations has led to identification of more reproductive-aged women who test positive for the mutation which might impact attitudes and decisions about relationships, childbearing and the use of preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND). A cross-sectional survey was administered to 1081 self-reported BRCA carriers to investigate how knowledge of BRCA status influences these issues. The mean age at BRCA test disclosure was 44years and 36% reported a personal history of cancer. Of 163 women who were unpartnered, 21.5% felt more pressure to get married. Of 284 women whose families were not complete, 41% reported that carrier status impacted their decision to have biological children. Women with a history of cancer were more likely to report that knowledge of BRCA+ status impacted their decision to have a child (OR 1.8, 95% CI 1-3.2). Fifty-nine percent thought PGD should be offered to mutation carriers and 55.5% thought PND should be offered. In conclusion, knowledge of BRCA status impacts attitudes regarding relationships and childbearing, and most carriers believe that PGD and PND should be offered to other carriers. This study suggests that BRCA carriers desire and would benefit from reproductive counseling after test disclosure.

The clinical application of preimplantation genetic diagnosis for the patient affected by congenital contractural arachnodactyly and spinal and bulbar muscular atrophy.

To investigate the usefulness of preimplantation genetic diagnosis (PGD) for the patient affected by congenital contractural arachnodactyly (CCA) and spinal and bulbar muscular atrophy (SBMA). Multiple displacement amplification (MDA) was performed for whole genome amplification (WGA) of biopsied trophectoderm (TE) cells. Direct mutation detection by sequencing and next-generation sequencing (NGS)-based single nucleotide polymorphism (SNP) haplotyping were used for CCA diagnosis. Direct sequencing of the PCR products and sex determination by amplification of sex-determining region Y (SRY) gene were used for SBMA diagnosis. After PGD, the unaffected blastocyst (B4) was transferred in the following frozen embryo transfer (FET). In this PGD cycle, sixteen MII oocytes were inseminated by ICSI with testicular spermatozoa. Four blastocysts (B4, B5, B10, B13) were utilized for TE cell biopsy on day 5 after ICSI. After PGD, B4 was unaffected by CCA and SBMA. B5 was affected by CCA and carried SBMA. B10 was unaffected by CCA and carried SBMA. B13 was affected by CCA and unaffected by SBMA. B4 was the only unaffected blastocyst and transferred into the uterus for the subsequent FET cycle. The accuracy of PGD was confirmed by amniocentesis at 21weeks of gestation. A healthy boy weighing 2850g was born by cesarean section at the 38th week of gestation. PGD is a valid screening tool for patienst affected of CCA and SBMA to prevent transmission of these genetic diseases from parents to children.

WHAT ROLE SHOULD PUBLIC OPINION PLAY IN ETHICO-LEGAL DECISION MAKING? THE EXAMPLE OF SELECTING SEX FOR NON-MEDICAL REASONS USING PREIMPLANTATION GENETIC DIAGNOSIS.

In this article, we consider the prohibition on the use of preimplantation genetic diagnosis to select an embryo on the basis of its sex for non -: medical reasons. We use this as a case study to explore the role that public consultations have and should play in ethico-legal decision-making. Until the Human Fertilisation and Embryology Act 1990 was amended by the Human Fertilisation and Embryology Act 2008, non-medical sex selection of an embryo was not statutorily regulated, but it was the policy of the Human Fertilisation and Embryology Authority that such selection should not occur. However, since 2009, it has been a criminal offence to select an embryo on the basis of its sex for non-medical reasons. We consider the reasons given for this change and explore the role that 'public opinion' had in the decision-making process. On the face of it, asking the public what they think seems reasonable, fair and democratic, and those who are not in favour of public consultations being accorded great weight in matters of policy may appear out of touch and as wanting to impose their moral views on the public at large. But there are problems with doing so, especially when seeking to regulate ethically controversial issues. We discuss whether regulation should be influenced by public opinion obtained via 'public consultations', and utilise sex selection for non-medical reasons as an example of how (apparently) public opinion was used to support the criminalisation of this practice.

Public perspectives on the use of preimplantation genetic diagnosis.

To study the perspectives of the United States population towards the use of preimplantation genetic diagnosis (PGD) in various clinical scenarios. Online cross-sectional population based questionnaire of a nationally representative sample according to age, gender, race/ethnicity, income, education and religion. A total of 1006 completed the questionnaire with an overall response rate of 94%. A majority supported PGD for diseases fatal early in life or those causing lifelong disability (72.9 and 66.7%, respectively); only 48.0% supported PGD for diseases that manifest late in life. Respondents were more supportive of PGD for genetic diseases if they were aware of PGD prior to the survey (OR = 1.64; CI = 1.13-2.39). However, a small proportion were in favor of genetically-based trait selection: 21.1% supported PGD for sex selection, 14.6% for physical traits and 18.9% for personality traits. Compared to women, men were nearly two- to three-fold more supportive of PGD for sex selection (OR = 1.65; CI = 1.20-2.78), physical traits (OR = 2.38; CI = 1.60-3.48) and personality traits (OR = 2.31; CI = .64-3.26). Compared to Caucasians, Asians (OR = 3.87; CI = 1.71-8.78) and African Americans (OR = 1.61; CI = 1.04-2.74) were more supportive of PGD for sex selection. In a nationally representative sample, a majority supported PGD to identify early onset diseases. We noted significant variation in opinions by sex, race, and education. There was more support among those with prior knowledge of PGD suggesting that education about PGD may foster favorable opinions. This study identifies public knowledge and attitudes that may be used to shape future research hypotheses and clinical policies.

The regulatory gap for preimplantation genetic diagnosis.

AbstractThe use of preimplantation genetic diagnosis, the powerful technique employed during fertility treatment to select embryos based on their genes, is currently unregulated in the United States—unlike in nearly all other countries where PGD is available. Of course, the analytical quality of the genetic tests, the laboratories where they are performed, and the technicians who carry them out are subject to the Clinical Laboratory Improvement Amendment requirements. And as the Food and Drug Administration prepares to begin regulating laboratory‐developed tests, including many genetic tests, the clinical validity of the tests may also need to be demonstrated. But neither CLIA nor the U.S. Food and Drug Administration is responsible for governing medical practice, and state law and the relevant medical associations have largely fallen silent on the questions of when and why PGD ought to be performed. The result of this regulatory lacuna is that while PGD was originally intended for screening embryos for severe heritable disorders, it is now also employed for a variety of more controversial purposes.

Prevalence of use of preimplantation genetic diagnosis in Unidade Clínica de Paramiloidose from Centro Hospitalar do Porto

The Familial Amyloid Polyneuropathy, with the world's largest focus in Portugal, is recognized by the National Board of Assisted Reproductive Technologies as a serious disease eligible for Preimplantation Genetic Diagnosis. This study aims to determine the prevalence of the use of Preimplantation Genetic Diagnosis in FAP carriers followed in Unidade Clínica de Paramiloidose, Centro Hospitalar do Porto, and to identify the associated factors. Between January and May 2013, a representative sample of Portuguese Familial Amyloid Polyneuropathy carriers, aged between 18 and 55 years, was systematically recruited. The analysis is based on 111 carriers with previous familial diagnosis, who reported having ever tried to get pregnant after 2001. Data on sociodemographic characteristics and use of Preimplantation Genetic Diagnosis were collected through a self-administered questionnaire. Proportions were compared using the chi-square test. Crude and adjusted odds ratios (OR) and the respective confidence intervals of 95% (95% CI) were estimated using multivariatelogistic regression. The prevalence of use of Preimplantation Genetic Diagnosis was 20.7% (95% CI: 13.6-29.5). After adjustment, a household income above 1000 '¬/month (OR = 11.87; 95% CI 2.87-49.15) was directly associated with the use of Preimplantation Genetic Diagnosis, while carriers with an individual diagnosis (OR = 0.15; 95% CI 0.04-0.57) and children born after 2001 (OR = 0.07; 95% CI 0.02-0.32) revealed a prevalence of use significantly lower than those with a individual diagnosis and children born before 2001. The low prevalence of use of Preimplantation Genetic Diagnosis, as well as the less frequent use of the technique by those with a lower household income, shows the importance of improving access to Preimplantation Genetic Diagnosis in the case of Familial Amyloid Polyneuropathy. This work contributes to increase the sensitivity of health professionals around the use and accessibility to Preimplantation Genetic Diagnosis among Familial Amyloid Polyneuropathy carriers.

The Limits of Procreative Liberty

Robert Sparrow (2013) presents a thoughtful analysis of the complexities of the use of preimplantation genetic diagnosis (PGD) for the prevention of intersex conditions. He makes a distinction betw...