Preimplantation genetic diagnosis for familial dysautonomia.

Familial dysautonomia (FD) is the most common congenital sensory neuropathy in Ashkenazi Jews, caused by a single major mutation in the IKBKAP gene. Effective management for this severe debilitating disease is still not available, making preimplantation genetic diagnosis (PGD) a useful option for at-risk couples to establish an FD free pregnancy from the outset. PGD was performed for a couple with a previous affected child with FD, using first and second polar body testing to preselect mutation-free oocytes, based on mutation analysis with simultaneous testing of two closely linked markers, D9S58 and D9S1677. Of 15 tested oocytes, 11 carried information about both polar bodies' genotype, of which seven were predicted to be free of the FD gene. Three embryos resulting from these oocytes were transferred back to the patient, resulting in a triplet pregnancy and the birth of three unaffected children confirmed to be free of FD. This is the first PGD for FD, providing an alternative for those at-risk couples who cannot accept prenatal diagnosis and termination of pregnancy as an option for avoiding FD.

Polar body-based preimplantation diagnosis for X-linked disorders.

Preimplantation diagnosis for X-linked disorders has been performed predominantly by gender determination, which, however, leads to the discarding of 50% unaffected male embryos. In an attempt to identify X-linked mutation-free embryos for transfer, the present authors introduced preimplantation genetic diagnosis (PGD), using a sequential first and second polar body analysis, as an alternative to gender determination. This method was offered to eight couples at risk for having children with X-linked disorders, including haemophilia B, fragile-X syndrome (FMR1), myotubular myotonic dystrophy (MTMD), ornithine transcarbamylase (OTC) deficiency and X-linked hydrocephalus. The first and second polar bodies were removed following maturation and fertilization of oocytes in a standard IVF protocol and analysed using a multiplex nested polymerase chain reaction (PCR), involving testing for mutations simultaneously with linked markers. Overall, 13 PGD cycles were performed, resulting in the detection of 25 embryos with the predicted mutation-free maternal contribution; these embryos were transferred back to the patients in all cycles, yielding four clinical pregnancies. Four children were born following these pregnancies, including three unaffected and one with misdiagnosis as a result of allele dropout (ADO), which was predictable in the case of FMR1. Presented results demonstrate the clinical usefulness of the specific polar body testing for X-linked disorders as an alternative to PGD by gender determination.

Successful Day 5 embryo transfer and pregnancies resulting after transport of embryos by air for biopsy and genetic analysis.

PURPOSE: Case studies of four in vitro fertilization (IVF) cycles where embryo transport by commercial airline followed by biopsy and genetic analysis with subsequent culture to Day 5 and resulting ongoing pregnancy. METHOD: Retrospective clinical case study of 4 patients requiring preimplantation genetic diagnosis (PGD) testing. Normally fertilized embryos were transported in a battery-powered portable incubator by commercial airline following evaluation for fertilization under controlled conditions from the Center for Assisted Reproduction, Bedford, Texas to the Reproductive Genetic Institute, Chicago, Illinois. Following Day 3 embryo biopsy and genetic analysis, embryos were transported back to the Center for Assisted Reproduction for Day 5 embryo transfer. RESULTS: Ongoing clinical pregnancy resulted for all patients receiving embryo transfer. CONCLUSION: These results demonstrate the feasibility of embryo transport by air for centers that do not have the in-house capabilities to perform genetic analysis. With successful pregnancies obtained through extended culture to Day 5, embryos requiring genetic analysis can be successfully transported by air, tested, and returned to the initial facility for embryo transfer without time restriction.

Neonatal outcome of preimplantation genetic diagnosis by polar body removal: the first 109 infants.

CONTEXT: Our center developed the technique of preimplantation genetic diagnosis (PGD) by sequential polar body removal (PBR) for the diagnosis of Mendelian disorders and aneuploidies. This study examines the obstetric and neonatal outcome of the first 109 live births after PGD by PBR. OBJECTIVE: To determine if there were any observable effects of PGD by PBR on perinatal morbidity and mortality, birth defects, and growth parameters. DESIGN: Data on perinatal outcome were gathered for the first 109 infants by parental reporting and confirmed by telephone interview and chart review when indicated. In infants >6 months old, a follow-up telephone interview was performed establishing the developmental milestones attained by the child. SETTING: A research center conducting an institutional review board-approved research protocol in PGD. PATIENTS: All patients who had PGD by PBR who had clinical pregnancies. MAIN OUTCOME MEASURES: Gestational age, mode of delivery, perinatal mortality, birth weight, birth length, the presence of birth defects, and developmental milestones. RESULTS: There was no significant decrease in birth length or weight, or the frequency of small for gestational age infants. No specific pattern of birth defects was observed. CONCLUSION: Thus far, there are no observable detrimental effects of PGD by PBR on children born after the procedure.