Subject(s)
Mutation/genetics , Preconception Care , Preimplantation Diagnosis/methods , Cystic Fibrosis/diagnosis , Cystic Fibrosis/genetics , Female , Fertilization in Vitro , Humans , Italy , Microsatellite Repeats/genetics , Oocytes/chemistry , Oocytes/ultrastructure , Polymerase Chain Reaction/methods , Polymorphism, Genetic , Pregnancy , beta-Thalassemia/diagnosis , beta-Thalassemia/geneticsABSTRACT
Preimplantation genetic diagnosis (PGD) for single gene disorders combined with human leukocyte antigen (HLA) matching has recently emerged as a therapeutic tool for stem cell transplantation in couples bearing an affected offspring. There may exist, however, several patient- or cycle-specific limitations for certain couples. This article documents data regarding experience of single gene disorders combined with HLA matching obtained at Istanbul Memorial Hospital, Turkey. The data were obtained from 20 couples undergoing 26 PGD-HLA cycles for thalassaemia (n = 23), Wiscott-Aldrich syndrome (n = 1) and acute lymphoblastic leukaemia (n = 2). A total of 206 embryos was biopsied on day 3 of embryo development and subsequently analysed. After the analysis, 26 (12.6%) of them were found to be both healthy and HLA compatible. In 16 embryo transfers performed, seven (43.7%) clinical pregnancies were obtained, one of which resulted in miscarriage. Ten of the 26 cycles started (38.4%) were cancelled due to a lack of suitable (mutation-free and/or HLA-compatible) embryos. The data suggest that application of PGD in combination with HLA typing is a promising therapeutic tool for an affected sibling.
Subject(s)
Genetic Diseases, Inborn/diagnosis , Histocompatibility Testing , Infertility/diagnosis , Preimplantation Diagnosis , Adult , Female , Genetic Diseases, Inborn/genetics , Humans , Infertility/genetics , Pregnancy , Pregnancy OutcomeABSTRACT
Preimplantation HLA matching has recently emerged as a tool for couples desiring to conceive a potential donor progeny for transplantation in a sibling with a life-threatening disorder. In this paper we describe a strategy optimized for preimplantation genetic diagnosis (PGD) of haemoglobinopathies combined with HLA matching. This procedure involves a minisequencing-based genotyping of HLA regions A, B, C and DRB combined with mutation analysis of the gene regions involved by mutation. Analysis of at least eight polymorphic short tandem repeat (STR) markers scattered through the HLA complex has also been included to detect potential contamination and crossing-over occurrences between HLA genes. The above assay can also be used for preimplantation HLA matching as a primary indication. The strategy was clinically applied for HLA matching in 17 cycles (14 for beta-thalassaemia, one for Wiscott-Aldrich syndrome and two for leukaemia). A reliable HLA genotype was achieved in 255/266 (95.9%) of the blastomeres. In total, 22 (14.8%) embryos were obtained that were HLA-matched with the affected siblings, 14 (9.4%) of which were unaffected and transferred back to the patients. Four clinical pregnancies were obtained, three of which (one twin, two singletons) are ongoing and were confirmed as healthy and HLA-identical with the affected children. Minisequencing-based HLA typing combined with HLA STR haplotyping has been shown to be a reliable strategy for preimplantation HLA matching. The major advantage of this approach is that the validation of a single assay can be done once and then used for the majority of the patients, reducing notably time needed for preclinical set-up of each case.
Subject(s)
Genetic Diseases, Inborn/diagnosis , HLA Antigens/genetics , Histocompatibility Testing/methods , Preimplantation Diagnosis/methods , Blastocyst/physiology , DNA Mutational Analysis , Embryo Transfer , Female , Humans , Major Histocompatibility Complex , Microsatellite Repeats , Polymorphism, Genetic , Pregnancy , Pregnancy OutcomeABSTRACT
Pregnancy among women receiving hemodialysis as a renal replacement therapy is rare and the chance of a successful delivery is relatively low. In this article, we present 3 cases of women conceiving either before or after the initiation of hemodialysis. The various risks of each pregnancy and the outcome are discussed as well as the latest management guidelines for pregnant dialysis patients.
