Скачать с ютуб My opinion on PGT-A| PGT-Aneupoidy पर मेरे विचार (disclaimer) в хорошем качестве

My opinion on PGT-A| PGT-Aneupoidy पर मेरे विचार (disclaimer)

@PGS Disclaimer: This is my personal opinion. People may not agree with me. Please be nice to my comment section. ref:Letters https://doi.org/10.1038/s41556-021-00... 1.Laboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY, USA. 2.The Center for Human Reproduction, New York, NY, USA. 3.The Foundation for Reproductive Medicine, New York, NY, USA. 4.Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria. 5.These authors contributed equally: Min Yang, Tiago Rito. e-mail: [email protected]; [email protected] Chromosomal instability leading to aneuploidy is pervasive in early human embryos1–3 and is considered as a major cause of infertility and pregnancy wastage. . Here we provide several lines of evidence that blastocysts containing aneuploid cells are worthy of in vitro fertilization transfer. First, we show clinically that aneuploid embryos can lead to healthy births, suggesting the presence of an in vivo mechanism to eliminate aneuploidy. Second, early development and cell specification modelled in micropatterned human ‘gastruloids’ grown in confined geometry show that aneuploid cells are depleted from embryonic germ layers, but not from extraembryonic tissue, by apoptosis in a bone morphogenetic protein 4 (BMP4)-dependent manner. Third, a small percentage of euploid cells rescues embryonic tissue in mosaic gastruloids when mixed with aneuploid cells. Finally, single-cell RNA-sequencing analysis of early human embryos revealed a decline of aneuploidy beginning on day 3. "Our findings challenge two current dogmas: that a single trophectoderm biopsy at blastocyst stage to perform prenatal genetic testing can accurately determine the chromosomal make-up of a human embryo, and that aneuploid embryos should be withheld from embryo transfer in association with in vitro fertilization." Although chromosomal mosaicism is common in human embryos derived from in vitro fertilization (IVF),most IVF centres consider the mosaic or aneuploid embryos to be abnormal, and thus withhold them from transfer into uteri. Indeed, more than 80% of these embryos contain aneuploid blastomeres, while only 12.5% of fertilized oocytes are aneuploid7 ; approximately 60% of embryos are euploid–aneuploid mosaic and only 22% are euploid8 . The use of preimplantation genetic testing for aneuploidy (PGT-A) before embryo transfer to screen out aneuploidy has been proposed to improve delivery rates and reduce miscarriages in association with IVF. and has become an increasingly common clinical practice. Whether PGT-A improves IVF outcomes has, however, remained controversial. The high false-positive and false-negative rates in PGT-A means that a substantial number of diagnosed aneuploid or euploid embryos are actually mosaic. As spontaneous and IVF pregnancies demonstrate similar levels of mosaicism (12% versus 6.3%), excluding all embryos containing aneuploid cells from transfer would therefore deprive patients of options. To test whether mosaic human embryos develop normally, we report on 32 women who underwent frozen-thawed embryo transfers with 77 blastocysts that were diagnosed as mosaic and aneuploid by PGT-A. Nine clinical pregnancies were established (28.2%) from these transfers, 4 of which miscarried (44.4% of pregnancies, 12.5% of cycles), and the remaining ones were delivered (15.6%; Supplementary Table 1). Characteristics of participants and IVF cycles are presented in Supplementary Table 2. Median age was 40.6±4.1 years. Our observed pregnancy and live birth rate matched or even exceed the national average of expected outcomes for age-matched individuals who did not use PGT-A diagnostics (18% pregnancy and 12% live birth rate at age 40). Interestingly, while all transferred embryos were aneuploid, prenatal chromosomal analyses performed with chronic villus biopsies (CVS) or amniocenteses in delivered pregnancies uniformly revealed normal karyotypes. Comprehensive chromosomal analysis on the products of conception from three participants who miscarried in the first trimester showed that two demonstrated the same chromosomal abnormalities as previously detected in the original PGT-A analysis of the transferred embryos (Supplementary Table 1, patients 8 and 9), while the third (patient 7) had a normal karyotype, indicating the elimination of aneuploidy and suggesting a different cause for her miscarriage. Furthermore, successful cases of transferring diagnosed mosaic embryos have been reported. Together, these clinical results unveil the developmental capacity of mosaic embryos, thereby supporting the possibility of a developmental rescue mechanism. Indeed, an innate ability of the embryo to select against aneu ploid cells has been demonstrated using a mouse model.    • MORE BAD NEWS FOR PGT-A TESTING