Reproductive management through integration of PGD and MPS-based noninvasive prenatal screening/diagnosis for a family with GJB2-associated hearing impairment.

A couple with a proband child of GJB2 (encoding the gap junction protein connexin 26)-associated hearing impairment and a previous pregnancy miscarriage sought for a reproductive solution to bear a healthy child. Our study aimed to develop a customized preconception-to-neonate care trajectory to fulfill this clinical demand by integrating preimplantation genetic diagnosis (PGD), noninvasive prenatal testing (NIPT), and noninvasive prenatal diagnosis (NIPD) into the strategy. Auditory and genetic diagnosis of the proband child was carried out to identify the disease causative mutations. The couple then received in-vitro-fertilization treatment, and eight embryos were obtained for day 5 biopsy. PGD was performed by short-tandem-repeat linkage analysis and Sanger sequencing of GJB2 gene. Transfer of a GJB2c.235delC heterozygous embryo resulted in a singleton pregnancy. At the 13th week of gestation, genomic DNA (gDNA) from the trio family and cell-free DNA (cfDNA) from maternal plasma were obtained for assessment of fetal chromosomal aneuploidy and GJB2 mutations. NIPT and NIPD showed the absence of chromosomal aneuploidy and GJB2-associated disease in the fetus, which was later confirmed by invasive procedures and postnatal genetic/auditory diagnosis. This strategy successfully prevented the transmission of hearing impairment in the newborn, thus providing a valuable experience in reproductive management of similar cases and potentially other monogenic disorders.

Assessment of sex chromosomes of human embryos arising from monopronucleus zygotes in in vitro fertilization and intracytoplasmic sperm injection cycles of Chinese women.

OBJECTIVES: To examine abnormal fertilization phenomena in blastomeres of embryos generated from conventional IVF and ICSI displaying a single pronucleus at the zygote stage. METHODS: 132 embryos from monopronuclear zygotes (1PN) generated from conventional IVF and ICSI were examined by FISH (fluorescent in situ hybridization) with X, Y dual color centromere probes. RESULTS: In the embryos that were obtained from conventional IVF, the percentage of diploid, monoploid and mosaic sex chromosome were 54.35, 23.91 and 21.74%, respectively. In the embryos from 1PN zygotes derived from ICSI, the percentage of diploid, monoploid and mosaic sex chromosomes were 31.51, 31.51 and 36.99%, respectively. For monoploid embryos, the ratio of XO was significantly higher than that of YO in both conventional IVF and ICSI groups. CONCLUSION: The results demonstrated that the majority of embryos derived from 1PN zygotes generated with conventional IVF or ICSI have a high incidence of aneuploidy. Furthermore, the sex chromosome diploid ratio of embryos from 1PN zygotes derived from conventional IVF was significantly higher than those generated from ICSI procedure in Chinese women. Nevertheless, the high proportion of aneuploid embryos suggests that such embryos should not be utilized for embryo transfer.