Preimplantation Genetic Diagnosis For Patients With Chromosome Structure Abnormalities

With the developing of assisted reproductive technique (ART) , the great advancement knowledge of the human reproduction recently has been achieved. A novel kingdom for prenatal diagnosis, preimplantation genetic diagnosis (PGD) has been developed with the improvement of molecular biology technique, especially molecular genetics combined with ART. PGD is a new approach of prenatal diagnosis for the genetic defect patient, also the earliest diagnosis, which put the prenatal diagnosis ahead of getting pregnancy. Parents can avoid from repeating spontaneous abortions with the help of PGD and wouldn't be placed in the difficult and complex position of selective abortion with common prenatal diagnosis.Chromosome abnormality is one of the important causes for infertility, including the number abnormality and the structure abnormality. The number abnormality was classified to euploidy and aneuploidy. Aneuploidy is the most common chromosome abnormality in humans, occurring in at least 0.3% of newborns, 4% of stillbirth and approximately 50% of spontaneous abortions.A great deal of chromosome abnormality is structure abnormal. Chromosome structure abnormality including trslocation, inversion, intracheomosomal rearrangements, microdeletion, et al. Translocatin and inversion are the main structure abnormality in population. Balance translocatin is the most common structure abnormality, occurring in at least 0.2% of newborns, and more in the-couples with infertility or spontaneous abortion. The people who have normal phenotype with chromosome structure abnormal is named by carrier. Some kinds of unbalance gametes were produced during germ cell meiosis. Unbalance gametes lead to repeated spontaneous abortion, fetal death, stillbirth, newborn death, deformity, mental retardation, et al. The rate of some abnormal type giving birth to a child with deformity or mental retardation reach 100%. Some male carriers are infertile because chromosome breakpoint affect the sperm generate. In the past, amniocentesis or chorionic villus sample enables cells and tissues to be collected from fetus for the genetic diagnosis, umbulas penentration and ultrasound examination of fetus was utilized to detect morphological indicator at early or mid-pregnancy. The patients perhaps face selective abortion except for the long time waiting.PGD was extended as the ideal technique which could solve the two difficult problems at the same time, one is reprodution, the other is genetic diagnosis. PGD for the chromosome structure abnormality ismuch more complicated and difficult than number abnormality. Among the nearly 6,000 cycles of PGD, the proportion of preimplantation genetic diagnosis for aneuploidy screening(PGD-AS) is about three fourths. PGD for chromosome structure abnormal is no more than 1,000 cycles.There are only one normal type and one balance type among six genotypes gamete of Robert translocation carrier and eighteen genotypes of common balanced translocation theoretically. Fluorescence in situ hybridization(FISH) is the main technique for the chromosome structure abnormality, which combined cytogenetics with molecular biology. The choice of proper probe is the key to PGD by FISH, also is the main limitation. The enumerated locus-specific probe is usually chosen for Robert translocation carrier, whole chromosome painting probe is chosen for female carrier, telomere probe is chosen for translocation carrier, case-specific breakpoint-spanning probe for translocations produced by few labs.Our study aimed at resolving the problem of infertility and repeated spontaneous abortion caused by chromosome structure abnormalities, to help patients got the unaffected offspring. FISH was used to perform PGD. The study was divided into three parts: the first part is clinical PGD by FISH using commercial probe. 10 PGD cycles were performed for eight couples.casel: 46, XX, t(15;19); case 2: 46, XY, t(1;12)(q24;q24); case 3: 46, XY, t(2;3); case 4: 46,XY, AZF gene absent; case 5:46,XX, had an affected child with X-linked genetic disease; case 6: 46, X...