O-195 Fetal ploidy status in pregnancy loss evaluated by cell-free fetal DNA in maternal blood versus direct sequencing of the pregnancy tissue

Abstract Study question Is cffDNA in maternal blood applicable for fetal ploidy evaluation early pregnancy loss, and what are the strengths limitations of method. Summary answer With a sensitivity ∼85% aneuploidies ∼93% specificity, cffDNA-based testing is robust method status PL. What known already Pregnancy loss (PL) an under investigated condition without precise prognostic models or evident treatments. From previous studies using karyotype chromosomal microarray analysis it described that approximately half PLs caused by aneuploidy, but international guidelines still refrain from recommending routine genetic Traditional cytogenetics expensive dependent on collection tissue containing chorionic to avoid inconclusive results contamination. Consequently, investigation lost fetus lacking most literature about PL couples currently not getting explanation their loss. design, size, duration As part prospective Copenhagen Loss (COPL) cohort, 1000 consecutive women with (spontaneous miscarriage, missed miscarriage anembryonic sac) before GA 22 weeks were recruited between Nov 12, 2020, May 1, 2022. Results first 333 used validate compared direct sequencing collected tissue. Additional 667 included evaluate performance result distribution Participants/materials, setting, methods Blood drawn STRECK © tubes treatment was initiated within 24 h after complete passage vacuum system if surgical treated home medically classified as fetal, villi unknown sequenced at University Copenhagen. Genome wide fraction DNA SeqFF performed Hvidovre Hospitals NIPT Center. Main role chance Among invited candidates, participation rate 73%. Mean age 33.9 years (SD 5.2). Gestational inclusion ranged 35 days 149 measured last menstrual period mean 70.5 16.5), 10 weeks+1 day. BMI 24.6 kg/m² 4.6) 233 (23%) conceived fertility treatment. In 19 (6%) initial women, failed practical psychological reasons. isolated 228 (73%) cases, 86 (27%) cases thereby high risk being contaminated. The 85% (95% CI 79–90), specificity 93% (88–96), accuracy 89% (85–92), Cohen’s coefficient 0.78 showing substantial agreement.112 (11%) total analyses due low (SeqFF<0.015 < 0.025) quality. instances conclusive result, 446 (50%) euploid, 405 (46%) aneuploid, 37 (4%) contained multiple aneuploidies. common abnormal karyotypes identified trisomy 16 (n = 91), monosomy X 86), 41). Limitations, reasons caution platform does report polyploidy, uniparental disomy, copy number variants found 10% PLs. Moreover, must be situ hours limiting window testing. Wider implications findings Considering difficulties collection, relevant introduce tissue-independent alternative. validity this study shows potential improve clinical management research field Trial registration H-18024745