Noninvasive preimplantation genetic testing for aneuploidy: Is the glass half-empty or half-full?

Noninvasiveness is a common theme across medical specialties in the 21st century. In obstetrics, noninvasive prenatal testing provoked paradigm shift clinical practice through sequencing of fetal cell-free DNA (cfDNA) maternal plasma. However, current for preimplantation genetic aneuploidy (PGT-A) requires trophectoderm biopsy, which entails technical challenges and embryo viability concerns. The possibility to overcome these issues reached horizon recent years, with discovery that cfDNA released by culture media during latest stages development offers new strategy assess genetically (1Leaver M. Wells D. Non-invasive (niPGT): next revolution reproductive genetics?.Hum Reprod Update. 2020; 26: 16-42Crossref PubMed Scopus (35) Google Scholar). utility this challenged article Hanson et al. (2Hanson B.M. Tao X. Hong K.H. Comito C.E. Pangasnan R. Seli E. al.Noninvasive exhibits high rates amplification failure poor correlation results obtained using biopsy.Fertil Steril. 2021; 115: 1461-1470Abstract Full Text PDF (2) This study compared concordance among 166 blastocysts well-established invasive PGT-A program vs. commercially available kit. Results showed low (62.7%) full chromosome between biopsy (59.6%). interesting work an important effort establish feasibility approach. limitation that, although specific commercial kit, did not use embryologic and/or conditions modified from those used PGT-A. particular, modification volume drop necessary concentrate improve rates; typically, drops should be 5–10 μL Scholar, 3Rubio C. Navarro-Sánchez L. García-Pascual C.M. Ocali O. Cimadomo Venier W. al.Multicenter prospective embryonic biopsies 1301 human blastocysts.Am J Obstet Gynecol. 223: 751.e1-751.e13Abstract (21) Scholar) rather than 30 Reducing does impair blastocyst (4Minasi M.G. Fabozzi G. Casciani V. Lobascio A.M. Colasante A. Scarselli F. al.Improved formation reduced volume: comparison three different on 1128 sibling zygotes.J Assist Genet. 2015; 32: 215-220Crossref (16) addition, assisted hatching was performed day as part routine PGT-A; would required fully protocol. reported show enhance release medium or rates. There are additional methodologic factors consider. Despite overall success (62.7%), were significantly higher when collected 6/7 (74.2%) 5 (17.6%). established parameter controlled every design obtain optimal quantity proper previous studies, percentage informative varied 55.6% 97.6%, lower range reflecting day-5 collection For concordance, rate 59.6% calculated proportion identical all chromosomes (assessing whole-chromosome aneuploidies). if estimated considering ploidy per (euploid/euploid aneuploid/aneuploid), most published studies Scholar), 74%. Prior ranging 33.3–89.1% Most other agree single factor highest impact presence contamination cumulus cells special precautions collection, particularly extra care taken after denudation. Such steps described Scholar); thus, it unclear whether cell minimized. Other require adaptation analysis whole-genome protocols well diagnostic rules algorithms applied analyse results. example, chaotic interpreted caution because they more likely reflect degradation storage chromosomal constitution (3Rubio Embryo vitro fertilization (IVF) laboratory constantly evolving. procedures IVF laboratories have incorporated extended later transfer embryos, sequential media, group culture, time-lapse incubators, others. Some changes implemented parallel optimization benefited vitrification. Notably, any technique has challenges, there two possible results: techniques can outcomes worsen them, depending expertise team, learning curve, how technology introduced laboratory. As key strategies (5Cohen J. Grifo J.A. Multicentre trial screening New England Journal Medicine: in-depth look at findings.Reprod Biomed Online. 2007; 15: 365-366Abstract (77) same rationale emerging approaches: optimize adapt interpretation results, understand potential value cfDNA. We see glass half-empty — ignoring sticking conventional half-full, acknowledging working its utility. Finally, existing date, biopsies, blastocysts, inner mass. ultimate goal predict corresponds result healthy baby. t assessed embryos euploid concordant discordant medium. limited number undergoing both sample types makes difficult draw definitive conclusions. underscores need nonselection randomized comparing morphology, will allow us real (e.g., ClinicalTrials.gov#NCT4000152). conclusion, evidence supports secrete medium, sequenced acceptable sufficient without contamination. directly Contamination timing influence Laboratory amplification, protocols, mandatory further advance technology. Target identification drug data-driven hypothesis experimental validation ovarian endometriosisFertility SterilityVol. 116Issue 2PreviewTo identify targets discover drugs endometriosis (OE) Full-Text