RESUMO
Mutations in mitochondrial DNA (mtDNA) are maternally inherited and can cause fatal or debilitating mitochondrial disorders. The severity of clinical symptoms is often associated with the level of mtDNA mutation load or degree of heteroplasmy. Current clinical options to prevent transmission of mtDNA mutations to offspring are limited. Experimental spindle transfer in metaphase II oocytes, also called mitochondrial replacement therapy, is a novel technology for preventing mtDNA transmission from oocytes to pre-implantation embryos. Here, we report a female carrier of Leigh syndrome (mtDNA mutation 8993T > G), with a long history of multiple undiagnosed pregnancy losses and deaths of offspring as a result of this disease, who underwent IVF after reconstitution of her oocytes by spindle transfer into the cytoplasm of enucleated donor oocytes. A male euploid blastocyst wasobtained from the reconstituted oocytes, which had only a 5.7% mtDNA mutation load. Transfer of the embryo resulted in a pregnancy with delivery of a boy with neonatal mtDNA mutation load of 2.36-9.23% in his tested tissues. The boy is currently healthy at 7 months of age, although long-term follow-up of the child's longitudinal development remains crucial.
Assuntos
Heterozigoto , Doença de Leigh/prevenção & controle , Terapia de Substituição Mitocondrial , Oócitos/ultraestrutura , DNA Mitocondrial/química , Feminino , Fertilização in vitro , Humanos , Doença de Leigh/genética , Nascido Vivo , Herança Materna , Mitocôndrias , Doação de Oócitos , Linhagem , Gravidez , Diagnóstico Pré-Implantação , Análise de Sequência de DNARESUMO
The consideration of surgery during pregnancy requires weighing the benefit of urgent surgery against the risk to mother and fetus. Surgery during pregnancy involves an increase in both maternal and fetal risks. Thyroid and parathyroid surgery involves physiological risks to both mother and fetus specific to the disease and function of these endocrine glands. Evaluation of a thyroid mass is similar in pregnant patients with ultrasound and fine-needle aspiration biopsy providing the most important information, while the use of radiographic imaging is severely constrained except when specifically required. In general, thyroid surgery can be delayed until after delivery except in cases of airway compromise or aggressive cancer. In contrast, parathyroid surgery is recommended during pregnancy to avoid adverse effects to the neonate.
