Analysis of HLA-G in Maternal Plasma, Follicular Fluid, and Preimplantation Embryos Reveal an Asymmetric Pattern of Expression

Abstract Soluble HLA-G (sHLA-G) secretion by human preimplantation embryos in culture has been associated with successful embryo development, and therefore has potential to serve as a noninvasive marker of embryo viability. We have examined the spatial and temporal expression of HLA-G in embryos of varying developmental competence and the role of maternal factors in human embryonic HLA-G expression. Embryos that reached blastocyst stage on day 5 showed a higher frequency of sHLA-G secretion than those at morula or arrested stages (p &amp;lt; 0.05). There was no significant difference in sHLA-G secretion between normal embryos and those diagnosed as chromosomally abnormal by preimplantation genetic diagnosis. HLA-G detected in maternal plasma and follicular fluid did not appear to correlate with HLA-G expressed in the embryo or embryo supernatants. Confocal microscopy analysis indicated that HLA-G protein expression in embryos was not homogeneous; mostly, it was confined to blastocysts localized on trophectoderm and trophectoderm projections. Single-particle fluorescent imaging analysis of HLA-G on the cell surface of JEG-3 cells showed that HLA-G particles were mostly monomeric, but dimeric and higher order oligomers were also observed. These results suggest that HLA-G play an important role in preimplantation embryo development. However, the observed expression of HLA-G in arrested and chromosomally abnormal embryos indicates that HLA-G testing should be used with caution and in conjunction with conventional methods of embryo screening and selection.</jats:p

Health of children conceived after preimplantation genetic diagnosis: a preliminary outcome study

A preliminary study was conducted on health of children conceived after preimplantation genetic screening and diagnosis (PGD). Forty-nine children were assessed with 66 matched naturally conceived (NC) controls. Primary outcome was neurodevelopmental screening, and secondary outcomes were evidence of other health problems and assessment of parent-child relationships. Study and control children were well matched across relevant socio-demographic variables. Growth parameters at mean age 18 months were normal. The mean Griffiths quotient was 102.7 (+/-13.1) (PGD) and 103.3 (+/-12.8) (NC), both of which were within the normal range, and did not differ significantly. PGD cases were more likely to be lighter, at <2500 g (12 children, 24.5% versus one child 1.5%, P < 0.0001) and born earlier than controls (38.2 +/- 2.6 versus 40.0 +/- 1.4 weeks; P < 0.0001), consistent with other similar studies. PGD families showed no evidence of excess stress in their relationship with their child. The PGD group had significantly higher scores on the warmth-affection sub-scale (P = 0.042), and significantly lower scores on the aggression-hostility and rejection sub-scales (P = 0.030) of the questionnaire. The study showed no major ill effects from PGD on the child health. A larger study is needed to confirm the validity of this conclusion

Preimplantation genetic diagnosis for Down syndrome pregnancy*

Objective: To evaluate the effect of preimplantation genetic diagnosis (PGD) conducted for women who had Down syndrome pregnancy previously. Methods: Trisomy 21 was diagnosed by using fluorescence in site hybridization (FISH) before embryo transfer in two women who had Down syndrome pregnancies. Each received one or two PGD cycles respectively. Results: Case 1: one PGD cycle was conducted, two oocytes were fertilized and biopsied. One embryo is of trisomy 21 and the other of monosomy 21. No embryo was transferred. Case 2: two PGD cycles were conducted, in total, sixteen oocytes were fertilized and biopsied. Four embryos were tested to be normal, six of trisomy 21, and one of monosomy 21. Five had no signal. Four normal embryos were transferred but no pregnancy resulted. Conclusion: For couples who had pregnancies with Down syndrome previously, PGD can be considered, and has been shown to be an effective strategy