Transfer of embryos with segmental mosaicism is associated with a significant reduction in live-birth rate

Abstract

Objective: To evaluate the impact of segmental mosaicism on pregnancy outcomes from the transfer of embryos previously designated as euploid. Design: Retrospective cohort analysis. Setting: Single, private, high-volume fertility center. Patient(s): Three hundred and twenty-seven women who underwent 377 frozen single euploid embryo transfers. Intervention(s): Trophectoderm biopsy of embryos cultured to the blastocyst stage, where all transferred embryos were designated euploid by high-density oligonucleotide array comparative genomic hybridization (aCGH); after ascertaining all outcomes, revaluation of aCGH results for evidence of segmental mosaicism (defined as mosaicism on a portion of a chromosome). Main Outcome Measure(s): Live-birth rate and spontaneous abortion rate. Result(s): Of the 377 embryos transferred, 357 were euploid with no mosaicism, and 20 embryos had segmental mosaicism. Segmental mosaics had a statistically significantly lower live-birth rate compared with euploid controls (30.0% vs. 53.8%). When controlling for age and day of Trophectoderm biopsy, the odds for live birth after transfer of segmental mosaics were reduced by 66% compared with euploid controls (0.34; 95% confidence interval, 0.13-0.92). The spontaneous abortion rate was statistically significantly higher after transfer of segmental mosaics compared with euploid controls (40.0% vs. 18.2%). Conclusion(s): Blastocysts with segmental mosaicism have reduced reproductive potential but retain the ability to result in live birth. These results support reporting segmental mosaicism to optimize selection of a single embryo for transfer that will maximize the chance of life birth. (Fertil Steril Ò 2019;111:69-76. Ó2018 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.

Noninvasive preimplantation genetic testing for aneuploidy in spent medium may be more reliable than trophectoderm biopsy

“…Although any risk of transferring a miscalled embryo is considered too great, false positives are particularly concerning as these may lead to discarding embryos that would otherwise lead to normal births. There are now several reports of healthy babies being born after transfer of embryos diagnosed as aneuploid or diploid/aneuploid mosaic (15)(16)(17), with some studies reporting a live-birth rate of over 40% (18,19). False negatives are also of concern, because their transfer may lead to either no pregnancy or, worse yet, an abnormal fetus.…”

Is cell-free DNA in spent embryo culture medium an alternative to embryo biopsy for preimplantation genetic testing? A systematic review

“…The similar amount of cf-DNA in SCM from aneuploid and euploid embryos suggests that both cell types undergo apoptosis during embryo development (Vera-Rodriguez et al, 2018). In some cases, aneuploid cells are extensively eliminated from the growing embryo, leading to embryo self-correction (van Echten-Arends et al, 2011;Bazrgar et al, 2013;Taylor et al, 2014;Greco et al, 2015;Sachdev et al, 2017;Zore et al, 2019). The finding that euploid embryos and healthy live births are obtained after the transfer of mosaic embryos supports the hypothesis of genetic self-correction by the embryo (Sachdev et al, 2017;Bazrgar et al, 2013;Greco et al, 2015;Zhang et al, 2019).…”

Preimplantation genetic testing for aneuploidy: A Canadian Fertility and Andrology Society Guideline

“…Indeed, there is accumulating evidence from multiple observational studies that the transfer of mosaic embryos can result in ongoing pregnancies and healthy live births (Fragouli et al, 2017;Greco et al, 2015;Lledó et al, 2017;Santiago Munné et al, 2017;Victor et al, 2019;Zhang et al, 2019;Zore et al, 2018). The opposite, misdiagnosing mosaic embryos as euploid and transferring them resulting in mosaic or abnormal pregnancies, is also possible.…”