ABSTRACT Objective To report on the development, validation, and clinical outcomes of 876 consecutive cases of prenatal diagnosis of rare monogenic diseases using celocentesis. Methods This retrospective single‐center study, conducted between April 2006 and December 2025, evaluated celomic fluid collected at 7–9 weeks of gestation from women at risk of carrying fetuses with monogenic diseases. Fetal DNA was obtained by isolating embryo‐fetal erythroid precursors. All samples were assessed for the presence of parental molecular defects and maternal cell contamination (MCC). Results The median gestational age at the time of celocentesis was 8.4 weeks. Successful aspiration of celomic fluid was achieved in 875/876 cases (99.9%). Although MCC was observed in 98.74% of the samples, an initial subset of 19/190 (10%) was found unsuitable for molecular analysis. Subsequently, an optimized molecular workflow was successfully applied to the remaining cohort, achieving a success rate of 98% (671/685 procedures). Results were validated against confirmatory samples from abortive tissue (following VIP), amniotic fluid, or postnatal blood. All cases were correctly classified, demonstrating 100% sensitivity and specificity. Conclusion This study supports the clinical application of celocentesis as a reliable early prenatal diagnostic procedure for monogenic diseases. It represents a viable alternative to Chorionic Villus Sampling (CVS) and amniocentesis, enabling invasive prenatal diagnosis at a significantly earlier stage of pregnancy.
Giambona et al. (Sat,) studied this question.