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.

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.

Hematopoietic Cell Transplantation (HCT) For Fanconi Anemia (FA): Comparable Outcomes Regardless Of Stem Cell Source

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3706-3706
Author(s):  
Margaret L. MacMillan ◽  
Todd E. Defor ◽  
John E. Wagner
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Genetic Diagnosis ◽  
Young Patients ◽  
Organ Function ◽  
Hematopoietic Stem ◽  
Vitro Fertilization ◽  
Sibling Donor ◽  
Matched Sibling

Abstract Historically, outcomes after alternative donor (AD)-HCT for FA have been strikingly inferior to those observed in recipients of HLA-matched sibling donor (MSD) hematopoietic stem cells (HSC) with excessive rates of graft failure, graft-versus-host-disease (GVHD), regimen related toxicity and infection, resulting in poor survival rates. Between 2006-2013, 44 FA patients with marrow aplasia and good organ function underwent AD-HCT after total body irradiation 300 cGy (single fraction) with thymic shielding, fludarabine (FLU) 140 mg/m2, cyclophosphamide (CY) 40 mg/kg and antithymocyte globulin (ATG). Outcomes were compared to those transplanted with HSC from an HLA matched sibling donor (n=24) after FLU 175 mg/m2, CY 20 mg/kg and ATG conditioning (1999-2013). GVHD preventative measures were identical with all recipients of marrow having the graft T cell depleted by CD34 selection (regardless of donor type) prior to infusion in addition to cyclosporine A and methylprednisolone or mycophenolate mofetil. Recipients of umbilical cord blood had no additional graft processing. Except for higher use of pre-HCT G-CSF in recipients of AD-HCT, patient characteristics were similar between the 2 groups. Probabilities of neutrophil recovery, acute and chronic GVHD were similar between the groups (Table 1). Most notably, probability of survival at 3 years was the same between the two groups (Figure 1). To our knowledge, this is the first demonstration of comparable outcomes after AD-HCT and MSD HCT for FA patients with marrow aplasia. These findings have three important implications: 1) timing for HCT need not be delayed if the patient lacks an HLA matched sibling donor, 2) potentially reduced enthusiasm for in vitro fertilization and preimplantation genetic diagnosis to have a 'savior sibling' and 3) ineligibility of FA young patients with a suitable AD (HLA matched adult volunteer or 5-6/6 matched UCB) and good organ function for high risk trials, including gene modified HSC. Disclosures: Wagner: Novartis: Research Funding.

Pre-implantation Screening and Diagnosis

2021 ◽  
Author(s):  
Kaylin O’Brien
Keyword(s):  
Preimplantation Genetic Diagnosis ◽  
Genetic Screening ◽  
Genetic Diagnosis ◽  
Preimplantation Genetic Screening ◽  
Diagnostic Methods ◽  
Vitro Fertilization ◽  
Blastomere Biopsy ◽  
Non Invasive ◽  
Gene Level

Through cellular biopsy of a developing embryo, genetic testing can be performed as part of the embryo selection phase of an in vitro fertilization (IVF) cycle. Preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD) allow embryos to be tested for genetic conditions on a chromosome and gene level, respectively, prior to implantation in the uterus and prior to pregnancy. Included in this review are indications for PGS and PGD, the biopsy and diagnostic methods that are most frequently utilized, advances in recent non-invasive technologies, and potential impacts that PGS/PGD and IVF may have on developing embryos. This review contains 5 figures, 1 table, and 53 references.  Keywords: Preimplantation genetic diagnosis, preimplantation genetic screening, blastocyst biopsy, blastomere biopsy, advances in PGS/PGD, indications for PGS/PGD, non-invasive embryo biopsy, infertility

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.

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