Preimplantation genetic diagnosis for a single gene mutation for succinate dehydrogenase subunit B (the genetic basis for malignant paraganglioma) with successful pregnancy

Purpose: To report the first successful case of the birth of normal baby using preimplantation diagnosis for hereditary paraganglioma (PGL) followed by embryo transfer and to emphasize the importance of using mild follicle stimulating hormone (FSH) stimulation for IVF in women with diminished oocyte reserve. Materials and Methods: The female partner had a baseline serum FSH of 16.5 mIU/mL and the male partner had the malignant hereditary form of the PGL - pheochromocytoma (PGL/PCC) syndrome related to a mutation of the nuclear mitochondrial enzyme, succinate-dehydrogenase enzyme (specifically the B subunit) (SDHB). He was suffering from the malignant transformation of these neuroendocrine tumors. Before his death, he wanted to enjoy for a short time a baby with his own genes but feared passing the SDHB autosomal gene mutation to their child. Results: Eight blastomeres from eight embryos biopsied on day 3 were tested for SDHB gene by polymerase chain reaction. These eight metaphase II oocytes were obtained following mild FSH stimulation (150 units from day 3). Intracytoplasmic sperm injection (ICSI) was performed using the frozen/thawed sperm of this 35year-old male suffering from a malignant pheochromocytoma. Five of the eight embryos were found to have mutations of the SDHB gene. Two embryos with normal SDHB were transferred and one resulted in a healthy baby. Genetic testing of the baby confirmed the absence of the SDHB mutation. Discussion: The successful pregnancy supports, but does not prove, the importance of using mild FSH stimulation in the presence of diminished oocyte reserve to inhibit the iatrogenic development of a much higher percentage of embryos with aneuploidy.