Effect of pericentric inversion of chromosome 9 on reproductive outcomes in assisted reproductive technology: a propensity score–matched cohort study

Background Pericentric inversion of chromosome 9 [inv (9)] is a common chromosomal polymorphism found in approximately 1-2% of the population. While inv(9) has been generally considered a benign variant, its potential effects on reproductive outcomes, especially in the context of assisted reproductive technology (ART), remain unclear. This study aimed to evaluate whether inv(9) affects embryologic and reproductive outcomes in ART cycles. Methods This retrospective cohort study included 40,502 ART cycles conducted between September 2008 to December 2023, of which 903 involved couples carrying inv(9) and 39,599 involved couples with normal karyotypes (NK). Propensity score matching (PSM) was used to balance baseline characteristics. The primary outcome was live birth rate (LBR), and secondary outcomes included biochemical and clinical pregnancy, miscarriage, and neonatal outcomes among live births (multiple births and low birth weight), and cycle parameters (oocyte yield, fertilization, and blastocyst formation rates). Results After 1:2 PSM, baseline characteristics were balanced between inv(9) and NK groups. Cycle outcomes, including oocytes retrieved (10.0 ± 7.8 vs 9.9 ± 7.5), fertilization, and blastocyst formation rates, were comparable. In fresh embryo transfer (ET) cycles, inv(9) carriers had a modestly higher live birth rate compared to NK couples (46.4% vs 41.2%; aRR = 1.13; 95% CI 1.01–1.27), while no significant differences were observed in frozen embryo transfer (FET) cycles (41.1% vs 40.0%; aRR = 1.04; 95% CI 0.93–1.17). Other pregnancy outcomes (multiple births, low birth weight, biochemical pregnancy, clinical pregnancy, and miscarriage) were similar between groups. No significant differences in live birth, clinical pregnancy, miscarriage, multiple births, or low birth weight were observed between male and female inv(9) carriers in either fresh or frozen cycles. Conclusions Pericentric inversion of chromosome 9 was not associated with adverse embryologic or reproductive outcomes in ART. These findings support the classification of inv(9) as a benign chromosomal variant and provide reassurance that its presence does not warrant additional intervention in couples undergoing ART.