scholarly journals Preimplantation genetic diagnosis (testing) for monogenic disorders: indications and ethics

2019 ◽  
pp. 13-25
Author(s):  
Е.В. Соловьёва ◽  
Л.П. Назаренко ◽  
Л.И. Минайчева ◽  
А.В. Светлаков
Keyword(s):  
Preimplantation Genetic Diagnosis ◽  
Single Gene ◽  
Genetic Diagnosis ◽  
Severe Form ◽  
Human Embryos ◽  
Vitro Fertilization ◽  
Monogenic Disorders ◽  
Hereditary Disorders ◽  
Standard Regulation

Преимплантационная генетическая диагностика (тестирование) (ПГД/ПГТ) моногенных заболеваний направлена преимущественно на предотвращение рождения ребенка с наследственным заболеванием посредством обследования эмбрионов до имплантации в лечебном цикле ЭКО (экстракорпорального оплодотворения). Строгим показанием для ПГД генной болезни служит высокий риск рождения ребенка с тяжелой формой многогенного заболевания при отсутствии противопоказаний и ограничений. С расширением показаний для ПГД и возможностей генетического тестирования возникают вопросы по нормативному регулированию и этической ответственности врача при проведении процедуры. Этические вопросы возникают, когда генетический риск ниже показателя, расцениваемого как высокий, заболевание не может быть однозначно отнесено к тяжелым, а также при рассмотрении возможности переноса аномального эмбриона. Этические аспекты ПГД рассмотрены с точки зрения базовых этических принципов: пользы и непричинения вреда, автономии, справедливости. В сравнении с пренатальной диагностикой, реализация этих принципов при ПГД сталкивается с рядом дополнительных сложных вопросов. Ценность эмбрионов человека, вероятность оставить супружескую пару без детей должны соотноситься с действительным риском и тяжестью возможного заболевания. Preimplantation genetic diagnosis/testing (PGD/PGT) for monogenic disorders is directed on prevention of the birth of the child with a hereditary disorders by means of testing embryos before implantation in IVF (in vitro fertilization). The high risk of severe form of a single gene disease is a strict medical indication for PGD for monogenic disorders at condition of contraindications and restrictions lack. Extension of PGD indications and genetic testing opportunities raises questions on standard regulation and ethical responsibility. Ethical questions are happening if a genetic risk is lower than the «high» or the disease cannot be classified as serious and if abnormal embryo transfer is proposed. Ethical aspects of PGD are considered in terms of basic ethical principles: beneficence, non-maleficence, autonomy and justice. In comparison with prenatal diagnostics, realization of these principles at PGD faces a number of additional difficult questions. The value of the human embryos and probability to have no children has to correspond to the valid risk and severity of a possible disease.

scholarly journals Preimplantation Genetic Diagnosis for Severe Albright Hereditary Osteodystrophy

2008 ◽  
Vol 93 (3) ◽  
pp. 901-904 ◽  
Author(s):  
Steven A. Lietman ◽  
James Goldfarb ◽  
Nina Desai ◽  
Michael A. Levine
Keyword(s):  
In Vitro Fertilization ◽  
Outcome Measures ◽  
Preimplantation Genetic Diagnosis ◽  
Genetic Diagnosis ◽  
Male Infant ◽  
Severe Form ◽  
Vitro Fertilization ◽  
Gnas Gene ◽  
Gnas Mutation

Abstract Context: Preimplantation genetic diagnosis (PGD) enables the selection of embryos without mutations for implantation and has not been described to our knowledge for mutations in GNAS. Phocomelia in a patient with Albright hereditary osteodystrophy (AHO) has also not been previously described. Objective: The aim of this study was to identify a GNAS mutation in a patient with a severe form of AHO and pseudohypoparathyroidism type 1a with phocomelia and to perform PGD on embryos derived by in vitro fertilization to deliver an unaffected infant. Design: A proband and his family are described clinically, the GNAS gene was sequenced to identify a novel mutation in the proband, and PGD was performed on embryos. Setting: The setting was in a tertiary-care hospital. Patients: The patients were from a single family in which the proband has a severe form of AHO. Interventions: Interventions were PGD and in vitro fertilization. Main Outcome Measures: The main outcome measures were the clinical phenotypes and GNAS gene sequences of the proband, embryos, and family members. Results: After PGD, three genotypically normal embryos were transferred back to the mother. Pregnancy ensued, and a healthy male infant was delivered at 36.5 wk gestation. The GNAS genes in the baby were confirmed as wild-type, and the infant is free of any signs of AHO. Conclusions: We describe herein a proband with AHO and severe skeletal deformities (including phocomelia) related to a novel GNAS mutation and the delivery of a male infant with homozygous normal GNAS genotype after PGD.

The Outcomes of Preimplantation Genetic Diagnosis Therapy in Treatment of β Thalassemia - a Retrospective Analysis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3783-3783
Author(s):  
Naveen Qureshi ◽  
Drucilla Foote ◽  
Rebecca Madore ◽  
Mark C. Walters ◽  
Sylvia Titi Singer ◽  
...  
Keyword(s):  
Preimplantation Genetic Diagnosis ◽  
Therapeutic Option ◽  
Single Gene ◽  
Genetic Diagnosis ◽  
Human Leukocyte ◽  
Hematopoietic Stem ◽  
Vitro Fertilization ◽  
Blastomere Biopsy ◽  
Sibling Donor

Abstract BACKGROUND: β thalassemia is one of the most common single gene disorders. Hematopoietic stem cell transplantation (HCT) from a human leukocyte antigen (HLA)-identical sibling donor is a curative option that minimizes the risk of graft-versus-host disease, compared to alternative donor HCT. In families that have an affected child, preimplantation genetic diagnosis (PGD) can be utilized to select an unaffected embryo that is HLA-identical. Briefly, this procedure requires in vitro fertilization, oocyte retrieval, fertilization and blastomere biopsy for preimplantation analysis and identification of unaffected HLA-identical embryos. After delivery, umbilical cord blood from the sibling donor is collected for HCT. In our institution, PGD has been pursued as a therapeutic option by families with thalassemia. The estimated cost of this uninsured procedure is $20,000 per cycle. METHODS: Families affected with β thalassemia who attempted PGD were identified and reviewed for indication, attempted cycles, successful pregnancy and transplantation outcome. RESULTS: Eight identified families affected by thalassemia underwent PGD. The diagnosis of their affected children included: 6 cases of β thalassemia major and 2 cases of transfusion dependent E β thalassemia patients. A total of 14 cycles of PGD were attempted, ranging from 1–4 attempts per family. Following successful identification of HLA-identical cells, 2 pregnancies occurred (1 early miscarriage, 1 successful delivery). This pregnancy resulted in the engraftment of a β thalassemia child. CONCLUSION: PGD including selection of HLA-identical sibling embryos is a novel, therapeutic approach for patients with β thalassemia. While this offers the possibility of recruiting a suitable donor for HCT, it is limited by significant financial and emotional burdens that it places on families affected with β thalassemia. Improvements in its efficiency and cost will make this a more viable option for affected families.

The Emerging Technology and Application of Preimplantation Genetic Diagnosis

1998 ◽  
Vol 26 (1) ◽  
pp. 7-16 ◽  
Author(s):  
Richard J. Tasca ◽  
Michael E. McClure
Keyword(s):  
Preimplantation Genetic Diagnosis ◽  
Dna Analysis ◽  
Single Gene ◽  
Genetic Diseases ◽  
Polar Body ◽  
Genetic Diagnosis ◽  
Chromosome Analysis ◽  
Blastocyst Stage ◽  
Vitro Fertilization

Efforts to improve the means to diagnose and treat human genetic diseases have a long history in biomedical research and medicine. Now, preimplantation genetic diagnosis (PGD) provides a new way to prevent the transmission of certain types of human genetic diseases to the next generation. It is an alternative to elective termination of pregnancies.PGD is used to test for genetic diseases that are due to defective single genes or abnormal chromosomes within days of fertilization and prior to the establishment of pregnancy. The procedure essentially begins with the biopsy of one or more cells of a cleavage stage or blastocyst stage preimplantation human embryo that has been produced by in vitro fertilization (IVF). In certain cases, PGD can be done on polar bodies—discarded by-products of egg formation containing excess chromosomes—of unfertilized eggs. Then, the cell(s), or a polar body, is placed into a tube for single gene analysis (DNA analysis by polymerase chain reaction (PCR)), or for chromosome analysis by spreading the nucleus of the cell on a microscope slide (fluorescence in situ hybridization (FISH)).

Problems and prerequisites for determining the legal regime preimplantation genetic diagnosis in Russian legislation

2019 ◽  
Author(s):  
N.A. Altinnik , S.S. Zenin , V.V. Komarova et all ,
Keyword(s):  
In Vitro Fertilization ◽  
Preimplantation Genetic Diagnosis ◽  
Human Embryo ◽  
Legal Status ◽  
Genetic Diagnosis ◽  
Legal Regime ◽  
Vitro Fertilization

Сurrent problems and prerequisites for the formation of the legal regime of pre-implantation genetic diagnosis (PGD) are considered in Russian legislation with account the existing approaches to determining the legal status of a “pre-implantation” embryo obtained in the framework of the in vitro fertilization procedure (IVF) are discussed. The authors substantiates the conclusion that it is necessary to legally determine PGD as one of the stages of using IVF, as well as establishing generally binding requirements for the procedure, conditions and features of this diagnosis, taking into account the need to minimize the damage caused to the human embryo.

Sign in / Sign up

Export Citation Format

Share Document