PREIMPLANTATION GENETIC DIAGNOSIS FOR A SINGLE GENE MUTATION FOR SUCCINATE DEHYDROGENASE SUBUNIT B (THE GENETIC BASIS FOR MALIGNANT PARAGANGLIOMA) WITH SUCCESSFUL PREGNANCY
AACE ePoster Library. Check J. 05/13/15; 97752; 123
Dr. Jerome Check
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Abstract
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Objective: To report the first successful case of the birth of normal baby using preimplantation diagnosis for hereditary paraganglioma 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.
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 paraganglioma – pheochromocytoma (PGL/PCC) syndrome related to a mutation of the nuclear mitochondrial enzyme, succinate-dehydrogenace 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 8 embryos biopsied on day 3 were tested for SDHB gene by polymerase chain reaction. These 8 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 35 year old male suffering from a malignant pheochromocytoma. Five of the 8 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: Donor sperm was not a personal option for this couple. The success 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. There are data suggesting that the reason for some centers reporting poor pregnancy rates following conventional or high dose FSH stimulation in the presence of low egg reserve is down regulation of certain FSH receptors producing factors necessary for proper events of meiosis especially meiosis II. Precedents are sometimes important in helping other patients/physicians choosing the best personal option for them – IVF with genetic probes vs. donor sperm for the SDHB mutation.
Conclusions: This seems to be the first reported case of successful pregnancy for the SDHB type of hereditary PGL/PCC syndrome following transfer of embryos determined by pre-implantation genetic diagnosis to be devoid of the SDHB mutation despite the presence of the autosomal dominant gene in a parent.
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 paraganglioma – pheochromocytoma (PGL/PCC) syndrome related to a mutation of the nuclear mitochondrial enzyme, succinate-dehydrogenace 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 8 embryos biopsied on day 3 were tested for SDHB gene by polymerase chain reaction. These 8 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 35 year old male suffering from a malignant pheochromocytoma. Five of the 8 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: Donor sperm was not a personal option for this couple. The success 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. There are data suggesting that the reason for some centers reporting poor pregnancy rates following conventional or high dose FSH stimulation in the presence of low egg reserve is down regulation of certain FSH receptors producing factors necessary for proper events of meiosis especially meiosis II. Precedents are sometimes important in helping other patients/physicians choosing the best personal option for them – IVF with genetic probes vs. donor sperm for the SDHB mutation.
Conclusions: This seems to be the first reported case of successful pregnancy for the SDHB type of hereditary PGL/PCC syndrome following transfer of embryos determined by pre-implantation genetic diagnosis to be devoid of the SDHB mutation despite the presence of the autosomal dominant gene in a parent.
Objective: To report the first successful case of the birth of normal baby using preimplantation diagnosis for hereditary paraganglioma 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.
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 paraganglioma – pheochromocytoma (PGL/PCC) syndrome related to a mutation of the nuclear mitochondrial enzyme, succinate-dehydrogenace 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 8 embryos biopsied on day 3 were tested for SDHB gene by polymerase chain reaction. These 8 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 35 year old male suffering from a malignant pheochromocytoma. Five of the 8 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: Donor sperm was not a personal option for this couple. The success 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. There are data suggesting that the reason for some centers reporting poor pregnancy rates following conventional or high dose FSH stimulation in the presence of low egg reserve is down regulation of certain FSH receptors producing factors necessary for proper events of meiosis especially meiosis II. Precedents are sometimes important in helping other patients/physicians choosing the best personal option for them – IVF with genetic probes vs. donor sperm for the SDHB mutation.
Conclusions: This seems to be the first reported case of successful pregnancy for the SDHB type of hereditary PGL/PCC syndrome following transfer of embryos determined by pre-implantation genetic diagnosis to be devoid of the SDHB mutation despite the presence of the autosomal dominant gene in a parent.
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 paraganglioma – pheochromocytoma (PGL/PCC) syndrome related to a mutation of the nuclear mitochondrial enzyme, succinate-dehydrogenace 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 8 embryos biopsied on day 3 were tested for SDHB gene by polymerase chain reaction. These 8 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 35 year old male suffering from a malignant pheochromocytoma. Five of the 8 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: Donor sperm was not a personal option for this couple. The success 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. There are data suggesting that the reason for some centers reporting poor pregnancy rates following conventional or high dose FSH stimulation in the presence of low egg reserve is down regulation of certain FSH receptors producing factors necessary for proper events of meiosis especially meiosis II. Precedents are sometimes important in helping other patients/physicians choosing the best personal option for them – IVF with genetic probes vs. donor sperm for the SDHB mutation.
Conclusions: This seems to be the first reported case of successful pregnancy for the SDHB type of hereditary PGL/PCC syndrome following transfer of embryos determined by pre-implantation genetic diagnosis to be devoid of the SDHB mutation despite the presence of the autosomal dominant gene in a parent.
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